Abstract 3144: Mapping the functional interactions at the tumor-immune checkpoint interface

Abstract

Abstract The interactions between tumor intrinsic processes and immune checkpoints can mediate the immune evasion by tumors and responses to immunotherapy. It is, however, challenging to identify functional interactions due to the prohibitively complex molecular landscape of the tumor-immune interfaces. We address this challenge with a statistical analysis framework, termed immuno-oncology gene interaction maps (ImogiMap). ImogiMap quantifies tumor-immune checkpoint interactions based on their co-associations with immune-associated phenotypes. The interactions are statistically validated for significance, robustness, and specificity. The outcome is a catalog of maps that quantify the interactions at the tumor-immune interface for diverse immune phenotypes and checkpoints. We demonstrate that applications of ImogiMap on immune checkpoints and T-cell dysfunction signatures genes recapitulates the previously reported interaction of SERPINB9 and immune checkpoints in the tumor microenvironment. Our analyses also suggest other immune checkpoint and T-cell dysfunction signatures interactions that are significantly associated with IFNγ expression in uterine corpus endometrial carcinoma and basal-like breast cancer. We also provide open-source software and a user-friendly web application to enable future applications and rapid adoption of ImogiMap. Such applications may guide the discovery of previously unknown tumor-immune interactions and help the identification of immunotherapy targets. Citation Format: Behnaz Bozorgui, Elisabeth K. Kong, Augustin Luna, Anil Korkut. Mapping the functional interactions at the tumor-immune checkpoint interface [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3144.