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.
