SITC 2019 Scientific Highlights - Nov. 9

The Society for Immunotherapy of Cancer (SITC) is pleased to present scientific highlights from the Nov. 9, 2019, sessions of the 34th Annual Meeting.

In vivo tracking of adoptively transferred T cells enabled by PET/CT

Flexible copper-64-nanoparticle-based cell labeling system allows for in vivo tracking of adoptively transferred T-cells by PET/CT

Abstract O1

A flexible system for radiolabeling and tracking adoptive cellular therapies was presented by Hólmfridur R. Halldórsdóttir, MSc (Technical University of Denmark). By labeling T cells in vitro using copper-64 ([64]Cu) micelles, which are self-assembled lipids, the team was able to noninvasively monitor the in vivo biodistribution of these radiolabeled cells over the course of 40 hours using positron emission tomography/computed tomography (PET/CT), and track their response to various therapeutic interventions.

Prior to in vivo imaging, the impact of micelles on T cells was tested. Viability and function of the T cells were not affected by the micelles. Throughout all in vivo studies, there was correspondence between the number of T cells in an organ and the measured radioactivity, indicating the cell tracking technique could provide accurate quantification. Following whole-body irradiation, elevated activity was noted in the thymus compared to non-irradiated mice, which is a well-known homing site for T cells after total body irradiation (4.6±0.1% vs 2.1±0.1% of injected dose, respectively). Tumors were also treated with a sustained release depot of TLR7 agonist, and, following this treatment, a higher accumulation of [64]Cu-labeled T cells was observed in the tumor tissues. This approach may therefore help elucidate the in vivo behavior of adoptive cellular therapies, without compromising their efficacy, which has immense implications for future monitoring of cellular therapies.

  

HER2-positive cancers may benefit from novel bispecific treatment

A phase 1 dose escalation study of PRS-343, a HER2/4-1BB bispecific molecule, in patients with HER2-positive malignancies

Abstract O82

Sarina Piha-Paul, MD (MD Anderson Cancer Center) presented an investigation of a HER/4-1BB bispecific, known as PRS-343, in patients with HER2-positive cancers. This dose-escalation study has evaluated cohorts from 0.0005 to 8 mg/kg in order to identify the safety profile of PRS-343 and to determine the dose for further studies. Measures of response and biomarkers were among the secondary objectives.

Fifty-three patients with solid tumors have been treated to date, and the minimal active dose was found to be 2.5 mg/kg. At and above this threshold, eighteen patients have been treated and are evaluable. In this patient group, significant expansion of the CD8+ T cell pool was noted after treatment with PRS-343, especially in the tumor microenvironment, in accordance with the proposed mechanism of action for PRS-343. This led to a disease control rate in these patients of 55%, including 2/18 patients confirmed partial response. Higher expansion of CD8+ T cells was found in responding patients over non-responders. The treatment was considered safe, with no serious adverse events or dose-limiting toxicities reported. The investigators are therefore continuing the further investigation of this first-in-class 4-1BB bispecific.

  

Front-line atezolizumab improves PD-L1+ NSCLC outcomes

IMpower110: Interim overall survival (OS) analysis of a phase III study of atezolizumab (atezo) monotherapy vs platinum-based chemotherapy (chemo) as first-line (1L) treatment in PD-L1-selected NSCLC

Abstract O81

PD-L1-postive NSCLC patients were treated with either front-line atezolizumab or chemotherapy in the IMpower110 study, presented by Giuseppe Giaccone, MD, PhD (Weill Cornell Medicine). In this study, both squamous and non-squamous NSCLC patients were enrolled, and randomized 1:1 to atezolizumab 1200 mg Q3W or platinum-based chemotherapy for four or six 21-day cycles. As the primary endpoint, overall survival was tested hierarchically by PD-L1 status (highest to lowest expression).

Across both arms of the trial, PD-L1 expression was evenly distributed: 37% of all-comers were TC3/IC3. The majority of patients experienced treatment-related adverse events: 60.5% of atezolizumab patients and 85.2% of chemotherapy patients reported any-grade events, with grade 3-4 in 12.9% and 44.1% as well, respectively. In patients with the highest levels of PD-L1 expression (TC3 or IC3), after a median follow-up of 15.7 months, the overall survival was significantly improved (by 7.1 months) with atezolizumab treatment over chemotherapy (HR=0.595, p=0.0106). The statistical endpoints were not met in the pre-specified next analysis group of TC2/3-IC2/3, however, so further analysis could not be performed for significance at other PD-L1 levels. Front-line atezolizumab may therefore hold promise for further exploration in highly-PD-L1-expressing NSCLC patients, who appear to derive the most benefit in this front-line study.

Microbial colonization linked to colorectal cancer immune responses

Helicobacter hepaticus remodels the tumor immune microenvironment and reduces colorectal tumor burden

Abstract O69

Based on the hypothesis that intestinal microbiota may modulate immune balance, Abigail E. Overacre-Delgoffe, PhD (University of Pittsburgh) presented a preclinical study of microbiome manipulation in colorectal cancer (CRC) models. Colitis-associated CRC was established through AOM-DSS induction, and half of these tumor-bearing mice were colonized with Helicobacter hepaticus (Hhep) after tumor development. Lymphocytes throughout the digestive tract and tumor were analyzed using flow cytometry and confocal microscopy.

Colonization of CRC tumor-bearing mice with Hhep was found to significantly remodel the tumor microenvironment, leading to increased dendritic and Tconv cell infiltration, as well as a decreased Treg presence. This also led to reduction of tumor burden and extension of overall survival for those mice supplemented with Hhep. Using FISH, Hhep was found to colonize not only the normal colonic mucosa, but also infiltrated tumors themselves as well. The authors report that the bacteria also lead to Hhep-specific CD4+ T follicular helper cell (Tfh) infiltration, which may contribute to more efficient anti-tumor immunity, particularly due to the increased number of organized tertiary lymphoid structures in the tumors. Further investigation of the microbiome may in turn provide insight and potential therapeutic mechanisms for improving anti-cancer immune responses.

Biomarkers for immunotherapy responsiveness in sarcomas defined

Immune enrichment and functional T-cell receptor (TCR) frequencies predict response to immune checkpoint blockade (ICB) in selected fusion-associated sarcomas

Abstract O33

Biomarkers of response to immunotherapy for sarcomas were analyzed and presented by Akash Mitra, BS (MD Anderson Cancer Center). Sarcoma patients (alveolar soft part and synovial) were treated with combination durvalumab and tremelimumab, and an in-depth analysis of tumor tissues was performed. Whole-exome, RNA- and TCR-sequencing were conducted to explore correlates with response.

Unlike some other cancer types, tumor mutational burden was not correlated with outcomes in this study. Rather, many immune-related pathways were upregulated in responders, as KEGG pathway analysis indicated higher activity of T cell and B cell response pathways, as well as increases in PD-L1. B cell infiltrates were also more frequent in responding tumors in both pre-treatment and on-treatment biopsies. T cell clonality was inversely correlated with outcomes, with an increased diversity in responders, and a lower maximum productive frequency in responders as well. While further immune deconvolution and BCR sequencing studies are on-going, these genetic and immune signatures may provide greater insight into the immune responsiveness of sarcomas.

Il-35+ B cells play a role in pancreatic cancer progression

IL-35+ B cells regulates anti-tumor immune response in pancreatic cancer

Abstract O47

Bhalchandra Mirlekar, PhD (University of North Carolina - Chapel Hill) presented a study of the immunologic processes that contribute to pancreatic tumor immunotherapy resistance. This involved the use of both spontaneous and orthotopic murine pancreatic tumor models, using a model with B cell-specific genetic loss of IL-35. Combination therapy of IL-35 blockade and immune checkpoint blockade was explored to further elucidate the role of IL-35.

This study uncovered an important role for regulatory B cells in the promotion of pancreatic tumorigenesis. Specifically, this cell population produced IL-35 – a cytokine which has been indicated in the suppression of T cell responses both in autoimmunity and cancer. The study further indicated that only B cell-produced IL-35 was essential for this immunosuppression to occur. When pancreatic tumors from the IL-35 deficient mouse model were treated with anti-PD-1 therapy, regression of normally immunotherapy-resistant tumors was observed. These preclinical studies were also corroborated through analysis of patient pancreatic cancer samples, in which an IL-35+ B cell subset was found, and correlated with dysfunctional T cells. IL-35-targeted therapy may therefore be promising for pancreatic cancer, but the model is still slightly disparate from the actual clinical situation. 

Bispecific anti-PD-1 and CTLA-4 antibody demonstrates promise of lower toxicity

A phase 1 study of AK104, a tetrameric bispecific antibody that targets PD-1 and CTLA-4 in patients with advanced solid tumors

Abstract O30

A dose escalation and expansion study of a PD-1/CTLA-4 bispecific antibody was presented by Ben Markman, MBBS, FRACP (Monash Medical Centre). While combination treatments of individual PD-1 and CTLA-4-targeting antibodies have shown encouraging efficacy, they are also limited by severe toxicities. Therefore, this group hypothesized that the bispecific tetrameric form of AK104 may maintain that efficacy while limiting toxicity due to enhanced tumor specificity. Patients with several solid tumor types were enrolled and dosed between 0.2 and 10 mg/kg Q2W with AK104 with the goal of determining the safety, efficacy, and recommended phase two dose of the treatment.

The bispecific agent was found to have a Kd an order of magnitude better than that of ipilimumab and nivolumab, supporting its improved targeting avidity. Fifty-five patients have been treated with a median of four doses as of data cut-off, with the most at the 6 mg/kg level. Any-grade treatment-related adverse events were reported in 63% of patients, with 11% of patients experiencing a grade 3 reaction, both of which compare favorably to the traditional combination therapy. When patients were treated with doses of at least 2 mg/kg, the overall response rate was 24%, and the disease control rate was 44%. Increases in Ki-67, a proliferation marker, were noted in peripheral CD4+ T cells after treatment with AK104, supporting immune activation. While it remains early to compare the efficacy of AK104 relative to currently-approved combination therapies, the initial safety profile of this agent warrants further investigation.

Immunologic responses noted in vaccine-treated glioblastoma

Phase II trial of therapeutic vaccine consisting of autologous dendritic cells loaded with autologous tumor cell antigens from self-renewing cancer cells in patients with newly diagnosed glioblastoma

Abstract O22

A patient-specific vaccine for glioblastoma patients, AV-GBM-1, was tested in a phase 2 study presented by Daniela Bota, MD, PhD (University of California – Irvine). The technique involved establishment of a short-term cell line from tumor tissue excised at the time of surgery, production of dendritic cells from PBMCs, and development of the vaccine antigens from irradiated tumor cell lysate. Vaccination was performed following completion of standard optimal therapy (surgical resection, radiotherapy, and chemotherapy). The study aimed to achieve a 75% survival rate fifteen months after enrollment, which would represent a 50% increase over survival from current standard therapies.

Thirty-one of the planned 55 patients have begun treatment, with success rates of 46/48 for cell line establishment and 41/42 for development of a successful leukapheresis product. To date, twelve patients completed all eight doses, and five discontinued early due to progression. Immunological responses including Th1, Th2, and Th17 responses were noted in 60% of patients for whom this was measured, indicating promising immune activation with this technique. No notable toxicities have been reported, with all serious adverse events not attributed to the treatment. The study is still ongoing, but, given the encouraging immune activation indications and safety profile so far, the authors are enthusiastic about future results.

SITC 2019 Scientific Highlights - Nov. 8

The Society for Immunotherapy of Cancer (SITC) is pleased to present scientific highlights from the Nov. 8, 2019, sessions of the 34th Annual Meeting.

Multiplexed ion beam imaging visualizes gastric irAEs

Gastric toxicity associated with PD-1 blockade therapy revealed by multiplexed ion beam imaging

Abstract O63

A gastric biopsy taken from a patient with nivolumab-associated gastroenteritis was analyzed using multiplexed ion beam imaging (MIBI) by Selena Ferrian, PhD (Stanford University) and colleagues. In order to develop a better understanding of the pathophysiology of this immune-related adverse event, twenty-seven labels were analyzed in a single upper gastric biopsy specimen.

The MIBI analysis visualized markers that were consistent with gastritis and revealed that interferon-gamma was being produced by gastric epithelial cells, rather than by immune cells. The tissue was characterized by a mixed inflammation profile, including both granzyme B-diminished/negative CD8 and FoxP3-diminished/negative CD4 T cells, with the majority of the T cells being CD4+. The investigators defined a set of features found in PD-1-associated gastritis, which included intense immune infiltrate into the lamina propria, interferon-gamma production by glandular epithelial cells, and high Ki67 expression by the epithelial cells as well. This in-depth study of a common immune-related adverse event may thus provide insight into the mechanisms of side effects and guide further immune checkpoint inhibitor development, through elucidating the mechanisms of inflammation and providing future drug targets.

CD27 T cell stimulation combination shows promise

Phase 1 study of an anti-CD27 agonist as monotherapy and in combination with pembrolizumab in patients with advanced solid tumors

Abstract O83

An anti-CD27 antibody, MK-5890, was tested in solid tumor patients in a study presented by Ronnie Shapira-Frommer, MD (Oncology Institute, Sheba Medical Center). Patients received either MK-5890 monotherapy or MK-5890 and pembrolizumab combination therapy, and monotherapy patients were eligible for cross-over upon disease progression. Endpoints of this study included safety and tolerability, with a secondary evaluation of objective response rate.

Forty-four patients were enrolled in the study: 25 received initial MK-5890 monotherapy at doses from 2-700 mg, while 19 were allotted to MK-5890 (200 mg) plus pembrolizumab.  Dose-limiting toxicities were observed in three of the monotherapy patients and one patient with the combination, all of which were related to infusion reactions. Over 90% of patients experienced some level of treatment-related adverse event, and grade 3-4 events were reported in 22.7% of the total population. In these initial cohorts, one patient in each group achieved a partial response. In monotherapy patients that then crossed over to the combination, adverse events were reported by 85%; at the same time, two of these patients exhibited a complete response, and another three partial responses with the median duration of the response not reached. Thus, costimulation of T cells through an anti-CD27 antibody may help improve anti-tumor activity of other therapies with further optimization, and the sequencing of CD27 stimulation appears to play a role in this efficacy.

PD-1-refractory patients may respond to TLR9 agonist

Durable responses in anti-PD-1 refractory melanoma following intratumoral injection of a toll-like receptor 9 (TLR9) agonist, CMP-001, in combination with pembrolizumab

Abstract O85

John M. Kirkwood, MD (University of Pittsburgh Medical Center) presented the results of a phase 1b study of pembrolizumab in combination with a TLR9 agonist, CMP-001, in patients with advanced PD-1 refractory melanoma. The majority of patients received combination pembrolizumab and CMP-001 (N=144), while a few were administered CMP-001 alone and allowed to cross-over (N=24). CMP-001, which is a CpG-A TLR9 agonist packaged into a virus-like particle, was intratumorally administered, and safety and efficacy were assessed.

The therapy was tested using a dose escalation/expansion strategy, with initial doses ranging from 1-10 mg CMP-001 (N=44), a first expansion cohort using 5 or 10 mg (N=69), and a second expansion using 10 mg (N=31). CMP-001 was also administered at two concentrations in the first expansion cohort. Overall, the treatment was well-tolerated, with the most common related adverse events being low-grade flu-like symptoms, and six patients discontinuing treatment due to adverse events. Across all cohorts, the ORR was 25%, while, among those receiving the diluted CMP-001 formulation, the ORR was 11%. Responses were noted in non-injected tumors, and, among those responding to the combination therapy, the median duration of response had not yet been reached. Response rates were similar whether a patient received monotherapy or the combination; however, the monotherapy responses were less durable. This combination therapy therefore holds promise to reverse PD-1 resistance in advanced melanomas, potentially through induction of an anti-viral immune reaction that is then able to eradicate tumors.

Prognostic B cell biomarkers identified

B-cell activated by checkpoint blockade immunotherapy and radiation improve overall survival in squamous cell carcinomas

Abstract O12

The importance of B cells in responses to immunotherapy and other cancer therapies was emphasized by Sangwoo Kim, BA (University of California – San Diego). This study evaluated B cell responses and biomarkers in HPV-associated head and neck cancer patient samples as well as in preclinical models. Proteomics arrays and RNA sequencing were employed in human samples (data from the Cancer Genome Atlas), while murine B cell responses were analyzed using BCR sequencing, flow cytometry, and single-cell RNA sequencing after combination treatment with radiotherapy and anti-PD-1 therapy.

The combination therapy in preclinical models was found to impact many aspects of B cell activity: systemic B cell activation, T1 and T2-type B cells, memory cells, plasma cells, and antigen specificity were all altered after the treatments. Specifically, BCR sequencing showed that combination therapy increased the maximum productive frequency and clonality, and also modified the CDR3 length. Increases in B cell germinal center development were also noted through single-cell RNA sequencing, with increasing density resulting from increasing treatment: more cells with a germinal center phenotype were observed with combination treatment over each individual monotherapy. In patient samples, combination therapy was found to increase IgG levels. Traditionally, HPV+ patients have demonstrated enhanced outcomes over their HPV- counterparts; however, this significance was abrogated after CD19 (marker for B cells) was taken into account, indicating that B cells play a major role in responses. For these reasons, the role of B cells in cancer biology and immunotherapy responsiveness merits further investigation and consideration, and development of adequate mouse models will be critical to achieving that goal.

Urinary microbiome linked to BCG response

Variation in the commensal urinary microbiome is associated with response to Bacillus Calmette-Guérin (BCG) immunotherapy in early stage urothelial bladder cancer

Abstract O67

The impact of the urinary microbiome on responses to intravesicular BCG therapy was investigated by Randy Sweis, MD (University of Chicago) and colleagues. Patients receiving BCG therapy experience a similar problem as has been observed with other immunotherapies: up to 50% of patients recur or progress within five years. Therefore, responsiveness to BCG therapy merits further investigation, as in this study. Sterile catheterization was employed to collect urine samples, and these samples were analyzed using 16S rRNA gene sequencing and shotgun sequencing for their microbial contents. Some samples were also analyzed for cytokine levels.

Thirty-one patients were enrolled and followed for a median of 12 months. In that time, 32% of patients recurred after transurethral resection and BCG instillation. Across all patients, the major phyla included Actinobacteria, Bacteroidetes, Firmicutes, Proteobacteria, and Tenericutes; however, distance matrix calculation revealed differences between patients with and without recurrence. Specifically, a higher abundance of Proteobacteria was found in recurring patients (P=0.035), with specific taxa showing even larger differences. At the same time, patients without a recurrence displayed higher levels of Firmicutes (P=0.049). Cytokine analysis in a subset of 13 patients revealed no significant differences between recurring and non-recurring patients. Therefore, the urinary microbiome may indeed have significant impact on the effectiveness of BCG therapy, just as the gut microbiome has been implicated with the effectiveness of other treatments.

CD73 antibody demonstrates immunomodulatory capabilities

Immunobiology and clinical activity of CPI-006, an anti-CD73 antibody with immunomodulating properties in a phase 1/1b trial in advanced cancers

Abstract O40

Phase 1 studies of an anti-CD73 antibody, CPI-006, were presented by Jason Luke, MD, FACP (University of Pittsburgh Medical Center), both as a single agent and in combination with ciforadenant. CPI-006 was administered every three weeks to patients with progressive cancer at doses from 1 to 24 mg/kg, with ciforadenant at a fixed 100 mg orally BID. The immunomodulatory activity of CPI-006 was evaluated through blood analysis of lymphoid subsets, IgH sequencing, and immunohistochemical analysis of tumor biopsies. 

Twenty-four patients received CPI-006 monotherapy, while sixteen received the combination. All-grade adverse events occurred in 75% of patients on both regimens, and grade 3-4 events in less than 17% of patients in both groups. A maximum tolerated dose was not determined. Through tissue occupancy studies, sustained CD73 occupancy in the periphery was found at doses at or above 6 mg/kg, and full tumor occupancy at 18 mg/kg or higher doses. Levels of circulating B and T cells were diminished 30 minutes after infusion, with B cells partially returning three weeks later, and T cell levels fully recovering. In alignment with a humoral immune response, the returning cells had a higher level of memory B cells than before treatment. In patients receiving at least 6 mg/kg CPI-006, tumor reductions were noted in 4/9 patients with RCC, NSCLC, or mCRPC, while no responses were noted in cancers without previous demonstration of sensitivity to these treatments. In addition to its therapeutic potential, the authors hypothesized that treatment with CPI-006 may provide opportunities for identification of novel anti-tumor antibodies due to the induced B cell dynamics.

EGFR-mut NSCLC patients may benefit from neoantigen vaccination

Neoantigen vaccination targeting shared epidermal growth factor receptor (EGFR) mutations induces clinical and immunological responses in non-small cell lung cancer patients

Abstract O18

Gregory A. Lizee, PhD (MD Anderson Cancer Center) presented a phase 1 trial of personalized neoantigen vaccination in non-small cell lung cancer patients. Peptides for vaccination were selected from predicted mutation-encoding neoantigens amongst 508 screened cancer-associated genes. Each of the 24 enrolled patients received at least 12 weekly immunizations in combination with topical imiqimod, and, if EGFR mutation positive (N=16), also had the option to continue on EGFR inhibitors.

Clinical responses were observed in seven patients on the study, all of whom were EGFR mutation-positive. Of these responses, 5/7 displayed T cell responses specific to EGFR neoantigens, and three also had responses to the L858R driver mutation.  The treatment regimen was well tolerated, and no adverse events of Grade 2-5 were observed. For EGFR mutation-positive patients, continuing on EGFR inhibitors was strongly associated with longer overall survival (13.8 vs 7.6 months for continuing vs stopping therapy, P=0.038), indicating a possible synergy between vaccination and EGFR inhibition. Therefore, vaccination may be able to overcome resistance to EGFR inhibitors in NSCLC patients.

Novel CD4+ T cell-DC interactions may lead to increased T cell activity in virally induced cancer

Intratumoral CD163+ DC amplify the type 1 immune response of CD4+CD161+ T cells in HPV16-associated cancers and are associated with better survival

Abstract O44

Several immune cell subtypes were analyzed in HPV16-associated cancers by Chantal Duurland, PhD (Leiden University Medical Center) and colleagues. HPV+ patients have increased survival compared to HPV- patients, thus the role of the immune response to these cancers should be better elucidated. High levels of CD4+CD161+ infiltrating T cells have been found in HPV+ tumors; therefore, the authors used a multi-level approach to understanding the importance of this unique subset of CD4+ T cells in the HPV+ tumor microenvironment. The authors also described a population of CD14-CD33-CD163+ cells, which were identified as dendritic cells (DCs). This subset of DCs was found to associate with strong T cell infiltrates and improved patient survival, similar to CD4+CD161+ T cells. Thus, there was an effort to understand the crosstalk of these two immune subsets in HPV+ disease. Further analyses demonstrated that activated CD163+ DCs generated higher levels of both IL-12 and IL-18 compared to their CD163- counterparts, which in turn induced a type 1 immune response by T cells. Likewise, supplementing patient-derived HPV16-specific CD4+ T cells with IL-12 and IL-18 enhanced their ability to produce interferon-gamma, and this was enhanced compared to the CD4+CD161- T cells. Thus, IL-12 and IL-18 produced by CD163+ DCs can increase stimulation of CD4+CD161+ T cells within the tumor microenvironment, which could ultimately contribute to the improved outcomes of patients with virally induced cancers. This study emphasizes the importance of studying other immune subsets in patient tumors that may ultimately lead to novel immunotherapeutic combinations.

Activated natural killer cell therapy may help Merkel cell patients

Final results from a phase 2 study using off-the-shelf activated natural killer (aNK) cells in combination with N-803, an IL-15 superagonist, in patients with metastatic Merkel cell carcinomaimaging

Abstract O19

Shailender Bhatia, MD (University of Washington) discussed a study of activated natural killer cells (aNK) in patients with Merkel cell carcinoma (MCC). The cellular therapy employed in this trial originated from a rare NK cell lymphoma, and required on-site expansion and activation by irradiation prior to administration. While MCC often responds to PD-1 blockade, nearly half of MCC patients display downregulation of MHC-I or other immune evasion mechanisms, causing them to be refractory to immune checkpoint therapy. Therefore, this group explored the use of aNK cell therapy in this population, as this treatment option is effective even in the absence of MHC-I.

Seven patients were treated – three with aNK therapy alone, and another four with aNK and N-803 (an IL-15 superagonist) combination therapy. The therapy was well-tolerated, without any treatment-related adverse events over grade 2. Two of the seven patients experienced objective responses. One patient, refractory to pembrolizumab, achieved a complete response on aNK monotherapy; however, after six months, the patient then relapsed. Re-challenge with pembrolizumab after this relapse resulted in a complete response ongoing at 36 months. These promising initial findings have led the investigators to begin other trials related to the aNK therapy as well, without the requirement for on-site processing to aid in the treatment’s feasibility.

Single-cell RNAseq links T follicular helper cells to improved outcomes in HNSCC

Transcriptional dissection reveals antitumor role of T follicular helper cells in head and neck cancer

Abstract O42

Anthony R. Cillo, PhD (University of Pittsburgh) and colleagues performed single-cell RNAseq analysis of more than 130,000 CD45+ cells sorted from PBMCs and TILs of immunotherapy-naive HNSCC patients both with and without HPV infection, as well as samples from healthy donors.

A unique T follicular helper (TFH)-like gene expression signature was observed in CD4+ Tconv cells in TILs from HPV positive patients whereas a mainly effector-memory signature was detected in TILs from HPV- patients. Immunofluorescence analysis showed tertiary lymphoid structures in HPV+ patient samples, further implicating a role for TFH in HNSCC. Analysis of patient data from the cancer genome atlas revealed that a high TFH signature was associated with extended progression-free survival, even after an multivariate analysis controlling for 9 covariates (hazard ratio=0.041, p=0.02). The increased understanding of the immune microenvironment of HNSCC from this study may provide guidance for development of future immunotherapies.

President's Message - November 2019

Dear Colleagues,

This week we anticipate welcoming 5,000 scientists, clinicians, industry professionals and others to the Society for Immunotherapy of Cancer’s 34^th Annual Meeting & Pre-Conference Programs (SITC 2019) in National Harbor, Md. Our society and our Annual Meeting have been growing rapidly for two key reasons; the unprecedented success of cancer immunotherapy in the clinic, and the hope and expectations we all share that continued research in our field will produce more effective treatments for patients. From the small group that formed the society in the early 1980s, we have now grown to almost 3,000 members. By working together to promote research, education and the careers of our members, we can achieve the primary goal of the Society, which is to improve the lives of cancer patients.

At SITC 2019, we will once again gather together to hear and discuss the latest research and to develop new ideas and collaborations for the lab and clinic. The depth and quality of cancer immunotherapy research at our upcoming meeting is evident in the nearly 1,000 abstracts submitted to SITC 2019, as well as the SITC 2019 late-breaking abstract titles. The meeting organizers have worked diligently to bring the best science to the meeting, and to make the meeting a forum for discussion of the latest clinical advances. Along these lines, I’m excited to announce that we’ve added a new session to the 34^th Annual Meeting programming on Saturday, Nov. 9, at 7 a.m., bringing together world experts to discuss the clinical implications of the most recent phase III immunotherapy trials in non-small cell lung cancer (more details are below). We hope you’ll join us!

On behalf of the society, I want to thank everyone who chose to bring their latest data to SITC 2019; I look forward to seeing your presentations this week in National Harbor and the engaging discussions that will follow.

Finally, I would also like to emphasize how much we value and appreciate the commitment of veteran and new members to our society. As we prepare to travel to National Harbor, I’d like to remind you that the 2019 SITC member dues cycle closes with the opening of our Annual Meeting & Pre-Conference Programs. Those who join SITC or renew their membership while attending SITC 2019 will receive the value of nearly 14 months of SITC membership. As a small token of appreciation, SITC members who renew their membership in National Harbor will also receive an exclusive SITC backpack and individuals who become a new SITC member will receive a society-branded water bottle. More information will be available when you arrive at SITC 2019 and receive your registration materials.

I look forward to seeing you all this week in National Harbor!

Sincerely,

Mario Sznol, MD
SITC President

President's Message - October 2019

Dear Colleagues,

In one month, the SITC family will gather once again, in National Harbor, Md., to hear the latest research in tumor immunology and cancer immunotherapy as presented by many of the world’s foremost experts in the field. I am looking forward to welcoming you all to this reunion, our society’s 34^th Annual Meeting & Pre-Conference Programs (SITC 2019). Regular abstract titles and author information were released on Tuesday, Oct. 1, and late-breaking abstract titles will be published on Nov. 1.

The complete SITC 2019 schedule continues to expand. There are so many reasons to attend; the latest advances in tumor immunobiology, state-of-the-art translational studies, results from early clinical trials, interactions with colleagues in government, academia, and industry, and of course, party with The CheckPoints. I’d like to highlight several recent additions to our annual event that will give you even more reasons to attend.

The first is a special session to focus on Lessons and Challenges from the Immunotherapy of Hematologic Malignancies: Informing the Next Generation of Cancer Immunotherapies. This is an exciting collaboration with the American Society of Hematology (ASH) and will kick-off the 34^th Annual Meeting proceedings on Thursday, Nov. 7, 2019, from 1-5 p.m. ET. We will also live stream the session to a global audience, inviting those to attend who cannot join us in National Harbor. I want to convey a special thank you to co-chairs, Katayoun Rezvani, MD, PhD (The University of Texas MD Anderson Cancer Center), and John M. Timmerman, MD (University of California, Los Angeles), who will lead the discussions during the session. To learn more about the session and to register for this live webcast opportunity, please click here.

Another highly anticipated program is this year’s Hot Topic Symposium on the final day of the SITC Annual Meeting, “Patient Impact on Immune Responses.” Chaired by Jennifer A. Ligibel, MD (Dana-Farber Cancer Institute) and Jennifer McQuade, MD, MS, MA, LAc (The University of Texas MD Anderson Cancer Center), this symposium will explore the many factors that can impact a patient’s anti-tumor immune response, including body mass index, gender, genetics, the microbiome and diet. A greater understanding of these factors will further personalize and optimize immunotherapy approaches for all cancer patients.

With what I believe reflects the excitement and promise of our field for cancer patients and our society’s efforts to advance the field and support our members, membership in SITC continues to grow. More clinical and laboratory investigators, clinicians, industry professionals and others are joining the SITC family than ever before! For this success we thank our members, prior leaders of SITC and the outstanding SITC staff. Welcome to the world’s leading organization dedicated to cancer immunotherapy; we’re happy to have you in the family!

Nonmembers who haven’t yet registered for SITC 2019 can become a SITC member very quickly and easily during the registration process. The deadline to receive the discounted registration rate to attend SITC 2019 is quickly approaching (Oct. 9, 2019), and the housing reservation deadline follows on Oct. 14, 2019. I appreciate the hard work of our organizers, faculty and staff as they complete their final preparations to ensure SITC 2019 is our society’s greatest conference yet.

Please be sure to visit the SITC booth during the Annual Meeting to join SITC or renew your membership. Those who secure their membership through the next calendar year while attending SITC 2019 will receive a special gift from the society.

I look forward to seeing you all in National Harbor, Md., next month.

Sincerely,

Mario Sznol, MD
SITC President

President's Message - September 2019

Dear Colleagues,

I’d like to begin this month’s President’s Message honoring Stan Collender (1951-2019). Stan, an immunotherapy pioneer and advocate, was a cancer patient of past SITC President Michael B. Atkins, MD. Dr. Atkins first met Stan in 2012 when he presented with Merkel Cell Carcinoma. From there, they developed a close relationship as Stan courageously fought his disease with immunotherapy for many years. Their experience and efforts together taught us much about the impact and limitations of immunotherapy. Read more about Stan’s life and contributions to our field in the heartfelt memorial posted by Dr. Atkins to The Sentinel, SITC’s official blog.

As you know, breakthroughs in research and the advent of new cancer immunotherapy treatments this century spurred an explosion of interest and investment in our field. Through offerings like the Annual Meeting & Pre-Conference Programs, the Society for Immunotherapy of Cancer (SITC) brings together the most accomplished and innovative researchers in the field to spark new collaborations and force consideration of new ideas that prompt discovery of new targets and approaches.

While the SITC Annual Meeting is perhaps our most important and visible effort to advance science and improve patient outcomes, many other SITC activities contribute to our core mission. SITC’s Advances in Cancer Immunotherapy™ (ACI) regional education series is an example of how SITC leverages its member’s clinical and science expertise to inform patient care, particularly safe and effective treatment administration. At the other end of the spectrum of SITC programs, the society seeks to expand research and knowledge in our field through the professional development of early career scientists. Young investigators are the future of cancer immunotherapy research. SITC is investing in their future through a variety of programs that provide education and professional development and promote community and collaboration.

One of our most effective programs aimed at young investigators is the SITC Meet-the-Experts – an annual luncheon at the SITC Annual Meeting (Thursday, Nov. 7, 2019, at 12:05 p.m.) organized by the Early Career Scientist Committee that connects young investigators with leaders in the field. It has now grown to a year-round initiative featuring regular, free webinars. These online events focus on various topics that are pertinent to an early career scientist’s professional development. Most recently, Tullia Bruno, PhD (University of Pittsburgh), moderated our Aug. 22 webinar focused on Careers in Science Away from the Bench, which you can view on-demand here.

SITC will once again host a Cancer Immunotherapy Winter School on Jan. 13-17, 2020, at the Hilton Houston Post Oak in Houston, Texas. Led by program organizers Lisa H. Butterfield, PhD (Parker Institute for Cancer Immunotherapy/University of California San Francisco), and Leisha A. Emens, MD, PhD (UPMC Hillman Cancer Center), this program provides intensive instruction on the core principles of tumor immunology and cancer immunotherapy. These programs also foster connections among peers which is critical component to their future success.

SITC also strengthens the support network for young scientists through the Professional Interest Communities. These digital discussion forums connect individuals of similar professional and personal backgrounds to share career development needs, address professional hurdles and more.

Beyond the basic education and professional development offered by SITC, SITC Fellowships provide funding to support the early careers of the most talented scientists. Supported through the Forward Fund, SITC has awarded more than $2 million in Fellowship Awards since 2014. Stay tuned later this year for information about 2020 SITC Fellowships.

SITC offers an affordable membership rate of $50 for students and scientists-in-training. Joining our society provides discounted access to vital SITC in-person programs and reduced fees on articles accepted to the Journal for ImmunoTherapy of Cancer (JITC). It also places young investigators in a professional network of the most influential basic scientists, translational researchers and clinicians in the field. Click here to become a SITC member and join the world’s leading organization dedicated solely to cancer immunotherapy research.

Finally, I would like to recognize and thank the countless number of women who organized, facilitated and attended SITC’s Women in Cancer Immunotherapy Network Leadership Institute in Seattle last month. This exciting new program from SITC, championed by immediate Past President Lisa H. Butterfield, PhD, was a rousing success. I look forward to seeing our society continue its effort to support, advance and celebrate the success of women in our field.

Sincerely,

Mario Sznol, MD
SITC President

President's Message - January 2019

Dear Colleagues,

I am excited and honored to address you in my first monthly message as President of the Society for Immunotherapy of Cancer (SITC). I have enjoyed the past two years as SITC’s Vice President, supporting Lisa H. Butterfield, PhD, SITC’s first female president, during her tenure as leader of our society. Thank you, Dr. Butterfield, for setting a foundation for the increased inclusion, development, and celebration of women in cancer immunotherapy. The society appreciates your continued leadership and commitment to the field and our organization!

As I assume this role on the heels of another successful year for SITC – which includes reaching new marks within our membership and a record-breaking 5,000 attendees at our Annual Meeting & Pre-Conference Programs – I am looking forward to helping continue our society’s tremendous growth. During my tenure as President, I will work to sustain SITC’s commitment as the leading member association in cancer immunotherapy. I will also ensure SITC remains the host to the most important meeting in the field, as we provide a platform for the presentation of phase 1 clinical trial data that provide insight into the future of immuno-oncology.

SITC has many exciting programs and initiatives slated for the next 12 months, all of which seek to improve cancer patient outcomes by advancing the science, development and application of cancer immunotherapy. A more complete listing of these initiatives is provided below, and I would like to highlight a few occurring in the near future.

It is critical for SITC to continue its emphasis in growing the next generation of leaders in cancer immunotherapy and tumor immunology. This is an area I am keenly focused on and support heavily. To that end, SITC is pleased to continue to offer SITC Fellowship Awards in 2019. Made possible through generous support from our industry partners, SITC Fellowships honor some of the brightest young minds in the field. The development and celebration of young investigators in our field is an important strategic priority of the society and one of my foci as President.

Additionally, registrations are open for SITC’s first Cancer Immunotherapy Winter School. Scheduled for Feb. 18-22 in Mesa, Ariz., this new program, tailored to early career scientists and clinicians as well as those new to the field, will teach the fundamentals of cancer immunotherapy and allow attendees to choose from a variety of tracks that focus on topics most relevant to them. Space is limited so register early! Also, SITC will host its first Meet-the-Expert Webinar on Thursday, Jan. 17 at 12:30 p.m. CST. This hour-long webinar, moderated by Sruthi Ravindranathan, PhD (Emory University), and with participation from presenter Vionnie W.C. Yu, PhD (Novartis Institutes for Biomedical Research), will focus on the topic Careers in Industry. Please click here to register for this free online event.

SITC continues its 2018-19 Advances in Cancer Immunotherapy™ (ACI) regional education program series, with events currently confirmed for Sacramento, Calif., on Jan. 10 in Houston on Feb. 9 and in Portland, Ore., on Feb. 21. Also, we look forward to hosting two, back-to-back thoughtful and engaging interim workshops, focused on cancer immune responsiveness and resistance; and adoptive cellular therapy. Stay tuned for information regarding location, registration and lodging.

If you haven’t already, I hope you’ll consider joining or renewing your SITC membership in 2019 to enjoy a variety of member benefits, including early access to register for the 34^th Annual Meeting & Pre-Conference Programs, scheduled for Nov. 6-10, 2019, in National Harbor, Md.

I am excited to strengthen existing, and build new, relationships with leaders in the field as we work together to continue the growth and success of the society.

Sincerely,

Mario Sznol, MD
SITC President