Abstract
The T cell-based immune system has evolved to recognize and destroy cells that differ from “self” on the basis of the antigens they express. Many human tumors contain large numbers of mutations, of which many hundreds can be present within expressed genes. As the resulting altered protein sequences are foreign to the immune system, immune recognition of such “neo-antigens” has been proposed as a major factor in the activity of clinically used immunotherapeutics such as anti-CTLA-4 and anti-PD-1.
In support of this hypothesis, using in-house developed technologies we have demonstrated that both CD4 and CD8 T cell recognition of the consequences of DNA damage is a common feature in human melanoma and can be boosted by T cell checkpoint blockade. Furthermore, to extend these data to other tumor types, we have benchmarked the foreign antigenic space in a variety of human cancers against a series of human pathogens. Collectively, these data, and data from other groups, establish “tumor foreignness” as one of the critical determinants in effective cancer immunotherapy.
Clearly, the sensitivity of tumor cells to the tumor-specific T cell pool that can be present in intrinsically foreign tumors forms an additional requirement for tumor control. To address factors that control such sensitivity, we a currently determining mechanisms of immune escape upon T cell targeting of human tumors. Results from this analysis are expected to contribute to the further definition of biomarkers that predict the outcome of the interaction between human tumors and the T cell-based immune system.
Citation Format: Ton Schumacher. T cell recognition and tumor resistance in human cancer [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr IA04.
