Dear JITC Readers,In the August edition of the JITC Digest, I would like to highlight the following articles. First, “The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck (HNSCC),” by Ezra E.W. Cohen et al. details the first new FDA approvals for patients with squamous cell carcinoma of the head and neck (HNSCC) since 2006, including the most recent 2019 approval of pembrolizumab as first-line treatment for patients with metastatic or unresectable, recurrent HNSCC in combination with chemotherapy for all patients or as monotherapy for patients with HNSCC whose tumors express PD-L1. These consensus guidelines serve as a foundation to assist clinicians’ understanding of the role of immunotherapies in this disease setting, and to standardize utilization across the field for patient benefit.
Furthermore, the article, “T cells expressing NKG2D chimeric antigen receptors efficiently eliminate glioblastoma and cancer stem cells” by Dong Yang et al. confirms the high expression of NKG2DLs in human glioblastoma cell lines, CSCs, and tumor samples and provides evidence that NKG2D CAR T cells effectively target glioblastoma cells and CSCs in an NKG2D-dependent manner, thus reporting on an encouraging therapeutic approach for glioblastoma patients.
Next, the research article entitled “Tumor-released autophagosomes induces CD4+ T cell-mediated immunosuppression via a TLR2–IL-6 cascade,” by Yong-Qiang Chen et al. reveals novel cellular and molecular mechanisms of tumor-derived extracellular vesicles in regulating CD4+ effector T cell function and pinpoints tumor cell-released autophagosomes (TRAPs) as a therapeutic target for cancer immunotherapy, specifically reporting HSP90-alpha on the surface of TRAPs as a novel target.
“Ovarian cancer stem cells and macrophages reciprocally interact through the WNT pathway to promote pro-tumoral and malignant phenotypes in 3D engineered microenvironments,” by Shreya Raghavan et al. details the hanging drop spheroid model developed to investigate pro-tumoral macrophage activation in response to CSCs and the role of WNT pathways in CSC-macrophage interactions. Such insight could provide new targets for reducing CSC-burden in ovarian cancer.
“HERA-GITRL activates T cells and promotes anti-tumor efficacy independent of Fc-gamma-R-binding functionality,” by David M. Richards et al. describes the development of a novel agonistic HERA molecule targeting GITR for which the underlying HERA-GITRL structure overcomes significant limitations of bivalent antibody-based approaches by mimicking the natural trimeric ligand, and thus inducing optimal trimeric assembly of the GITR receptors.
Finally, the clinical study, “First-in-human phase 1 study of IT1208, a defucosylated humanized anti-CD4 depleting antibody, in patients with advanced solid tumors,” by Kohei Shitara et al. reports on single agent IT1208, a humanized anti-CD4 immunoglobulin G1 mAb, which is shown to successfully deplete CD4+ T cells with a manageable safety profile and encouraging preliminary efficacy signals, warranting further investigations, possibly in combination with immune checkpoint inhibitors.
With best regards,
Pedro J. Romero, MD
Editor-in-Chief, Journal for ImmunoTherapy of Cancer
To view the entire August 2019 JITC Digest, please click here.
