Incoming tumor-reactive cytotoxic T lymphocytes (CTL) are modulated by innate immune cells of the tumor microenvironment and we have used intravital live-imaging to characterize the predominant T cell-APC interactions there. To further hone in on the identities of the APC populations, we have extensively examined myeloid subset diversity across multiple spontaneous (GEMM) and ectopic models. Importantly, as a functional counterpart to the abundant tumor infiltrating macrophages, we have identified a small population of rare tumoral Dendritic Cells capable of robust antigen processing and T cell stimulation. We have identified the specific lineage requirements of these cells, dissecting the essential cytokines driving each tumor APC population. In addition we have found that T-cell dependent immune clearance relies upon these rare tumoral Dendritic Cells. Thus, through the dissection of the tumor myeloid compartment we have revealed a rare, yet highly stimulatory and targetable DC subset that could be exploited therapeutically to enhance anti-tumor immune responses locally.
This work is supported by the Genentech Foundation and the Margaret A. Cunningham Immune Mechanisms in Cancer Research Fellowship Award.
Citation Format: Miranda Broz, Mikhail Binnewies, Bijan Boldajipour, Amanda Nelson, Joshua Pollock, David Erle, Andrea Barczak, Michael Rosenblum, Adil Daud, Diane Barber, Sebastian Amigorena, Laura J. van 't Veer, Anne Sperling, Denise Wolf, Matthew F. Krummel. Dissecting the tumor myeloid compartment reveals rare activating antigen presenting cells, critical for T cell immunity. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr B65.
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