JITC Letter from the Editor - October 2019

Dear JITC Readers,

I am pleased to share news of the launching of JITC’s very own Twitter handle (@JITCancer). Managed by JITC’s very own editors, this new platform will provide followers with access to JITC’s latest publications as well as cutting-edge news from throughout the fields of tumor immunology and cancer immunotherapy. Furthermore, it will give authors, readers, and editors a place to connect more directly on a global level.

If you use Twitter, please take a moment to follow @JITCancer and explore its social content. The October edition of the JITC digest also contains several highlighted articles that may be of interest for you to share with your followers. In particular, these highlighted articles show how insight into the interplay between malignant cells and the immune system can unlock new therapeutic strategies and diagnostic tools.

Two papers reveal new insight into which patients may benefit from checkpoint inhibition. The first, “Closed system RT-qPCR as a potential companion diagnostic test for immunotherapy outcome in metastatic melanoma” by Swati Gupta et al., develops a profile based on mRNA expression signatures of four genes (CD274 (PD-L1), PDCDILG2 (PD-L2), CD8A, and IRF1) that correlates with clinical outcomes in melanoma patients treated with anti-PD-1 immunotherapy. With further development, the approach they describe could offer a rapid-turnaround companion diagnostic, without standardization and threshold issues inherent in immunohistochemistry-based diagnostics.
The second article addresses the ongoing question of how T cell responses determine outcomes of checkpoint inhibition. Fehlings et al. shine some light on this issue by identifying a distinctive population of neoantigen-specific CD8+ effector-like T cells in PBMCs from patients with non-small cell lung cancer who responded to anti-PD-L1 treatment. Their findings are described in, “Late-differentiated effector neoantigen-specific CD8+ T cells are enriched in peripheral blood of non-small cell lung carcinoma patients responding to atezolizumab treatment.”

T cell engineering has emerged as an exciting new clinical frontier, with the marked success of chimeric antigen receptor (CAR)-based therapies. In, “A TIGIT-based chimeric co-stimulatory switch receptor improves T cell anti-tumor function,” Hoogi et al. deploy a novel T cell engineering strategy, generating a chimeric costimulatory switch receptor (CSR) that circumvents inhibitory signaling in the cancer milieu by fusing the extracellular ligand-binding domain of the co-inhibitory receptor TIGIT to the intracellular stimulatory domain of CD28. T cells co-transduced with both an antigen receptor and the CSR displayed enhanced cytokine production in vitro and prolonged survival in xenograft models of established melanoma.

The final paper highlighted in this month’s digest describes encouraging results from a phase 1 trial of a humanized anti-IL-8 monoclonal antibody in 15 patients with incurable metastatic or unresectable, locally advanced solid tumors. Bilusic et al. demonstrate that IL-8 blockade is safe and well-tolerated in, “Phase I trial of HuMax-IL8 (BMS-986253), an anti-IL-8 monoclonal antibody, in patients with metastatic or unresectable solid tumors.” What’s more, 11 out of 15 patients achieved stable disease, an encouraging result for ongoing studies investigating IL-8 blockade in combination with checkpoint inhibition.

With best regards,

Pedro J. Romero, MD
Editor-in-Chief, Journal for ImmunoTherapy of Cancer

To view the entire October 2019 JITC Digest, please click here. 

JITC Letter from the Editor - May 2019

Dear JITC Readers,

In the May edition of the JITC Digest, I would like to call your attention to the following five articles of special interest. First, “Determinant roles of dendritic cell-expressed Notch Delta-like and Jagged ligands on anti-tumor T cell immunity” by Elena E. Tchekneva et al. investigates the specific roles of Notch ligands in modulating T cell responses through genetic and pharmacological approaches in mouse models of lung and pancreatic tumors and cardiac allograft rejection. This study emphasizes the importance of specific expression of Notch ligands on dendritic cells by revealing their distinct roles in the regulation of T cell immunity, and suggests opportunities for modulating immune outcomes using engineered Notch ligand constructs.

Next, “Effective cancer immunotherapy by natural mouse conventional type-1 dendritic cells bearing dead tumor antigen,” by Stefanie K. Wculek et al. discusses the potential of using natural conventional type 1 DCs (cDC1s) as a syngeneic vaccine in cancer therapy and in a proof-of-principle study, demonstrates the feasibility and efficacy of a personalized anti-cancer treatment based on cross-presenting cDC1-based vaccination that does not require identification of tumor neoantigens. Such results provide valuable pre-clinical data regarding the efficacy of therapeutic cDC1-based anti-cancer vaccination for the development of next-generation DC vaccines.

Furthermore, the article, “CEA expression heterogeneity and plasticity confer resistance to the CEA-targeting bispecific immunotherapy antibody cibisatamab (CEA-TCB) in patient-derived colorectal cancer organoids,” by Reyes Gonzalez-Exposito et al. describes the benefits of using 3D in vitro patient derived organoid (PDO) models in place of patient cells lines to better represent the biological characteristics of patient tumors. The authors assess carcinoembryonic antigen (CEA) expression heterogeneity as a common finding in colorectal cancer PDOs from therapy resistant metastatic CRCs and the possible mechanisms by which resistance to cibisatamab immunotherapy may occur.

“Exploring the emerging role of the microbiome in cancer immunotherapy,” by Jessica Fessler et al. examines recent research on the bacterial component of the microbiota, the connection between certain bacteria and the process of carcinogenesis, as well as implications for how the microbiota may be modulating the efficacy and toxicity of cancer immunotherapy. Importantly, this review suggests future clinical implications involving exploitation of the host-microbiome interdependency for delivery of more potent therapy.

Finally, Marjolaine Debant et al.’s article, “STIM1 at the plasma membrane as a new target in progressive chronic lymphocytic leukemia,” extensively analyzes calcium entry in CLL cells, revealing that in patients with progressive disease, calcium signaling deregulation may be due to a constitutive and B cell receptor (BCR)-independent calcium entry pathway involving membrane-associated STIM1. This study warrants further evaluation of a mAb targeting STIM1PM in cancer therapy alone or in combination.

With best regards,

Pedro J. Romero, MD
Editor-in-Chief, Journal for ImmunoTherapy of Cancer

To view the entire May 2019 JITC Digest, please click here. 

Get to Know Sentinel Author: Saman Maleki, PhD

Name: Saman Maleki, PhD

Maleki

Title: Research Associate

Employer: Lawson Health Research Institute, London, Ontario, Canada

When and why did you become a SITC member?

I become a SITC member last year after I found out about all the great educational work SITC has been doing on the field of cancer immunotherapy.

Can you briefly explain the work you are doing in the field?

I am involved in several translational immunotherapy projects. We are studying the neoantigens in tumors and how it shapes the anti-tumor immune response. We are also studying indoleamine 2,3-dioxygenase (IDO) and its effect on immunotherapy and conventional therapy. I am also involved in pre-clinical IND-enabling studies of several novel oncology drugs including a few immuno-oncology agents.