Abstract 3843: Autologous resconstitution of human cancer and immune system in vivo

Correlative studies from checkpoint inhibitor trials have indcated that better understanding of human leukocytic trafficking into the human tumor microenvironment can expedite the translation of future immune-oncologic agents. In order to directly characterize signaling pathways that can regulate human leukocytic trafficking into the tumor, we have developed a completely autologous xenotransplanation method to reconstitute the human tumor immune microenvironment in vivo. When we analyzed the TCGA database of human head and neck squamous cell carcinoma(HNSCC), we found that STAT3 signaling was associated with worse prognostic mesenchymal subtye. We silenced STAT3 signaling in the tumor compartment in these autologously reconstituted humanized mice, and we noted increased tumor infiltrating lymphocytes and slower tumor growth rate. We also used this novel agents that can alter endogenous leukocytic infiltration into the tumor. Taken together, we present a valuable method to study individialized human tumor microenvironments in vivo without confound allgeneic responses. Citation Format: Juan Fu, Rupashree Sen, David L Masica, Rachel Karchin, Drew Pardoll, Young Kim. Autologous resconstitution of human cancer and immune system in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3843. doi:10.1158/1538-7445.AM2017-3843