Abstract A12: Identification of resistance to immune checkpoint blockade

Despite its enormous success in treating several types of cancer, including melanoma, lung cancer, renal cancer, bladder cancer, and Hodgkin’s lymphoma, immunotherapy still only induces responses in a subset of patients. Understanding the response and resistance mechanisms are still open questions. Based on the reported heterogeneous response to targeted therapies in multiple cell lines, we hypothesize that significant heterogeneity might also exist regarding the response to immune checkpoint blockade (ICB), which may manifest the mechanisms of response/resistance to ICB. To this end, we applied the ClonTracer barcoding system to assess the heterogeneity of response to anti-PD1 and anti-CTLA4 in CT26 colorectal cancer model. Surprisingly, whereas significant heterogeneity exists in the cell line’s ability to initiate cancer in vivo, ICB treatment did not lead to dramatic clonal enrichment compared to control treatment. Therefore, the tumor microenvironment and/or the epigenetic programs in cancer cells may dictate the response to ICB. Note: This abstract was not presented at the conference. Citation Format: Shengqing Stanley Gu Gu, Ziyi Li, Xia Bu, Xiaofang Xing, Gordon Freeman, Myles Brown, Xiaole Shirley Liu. Identification of resistance to immune checkpoint blockade [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr A12.