Abstract IA07: ER stress responses as new immune checkpoints in cancer

Abstract Harnessing the intrinsic ability of our immune system to eliminate malignant cells represents the most promising anticancer strategy since the development of chemotherapy. However, cancer cells employ diverse strategies that enable them to thrive under adverse conditions while simultaneously inhibiting antitumor immune responses. Diverse microenvironmental conditions within tumor masses, such as hypoxia and nutrient deprivation, disturb the protein-folding capacity of the endoplasmic reticulum (ER) and provoke a cellular state of “ER stress.” Sustained activation of ER stress sensors endows malignant cells with greater tumorigenic, metastatic, and drug-resistant capacity. Interestingly, recent studies demonstrate that tumor-infiltrating immune cells also experience ER stress, and that this process causes severe immune cell dysfunction and immunosuppression in cancer hosts. Aggressive ovarian cancers, for instance, cripple protective immunity by inducing excessive activation of the IRE1-XBP1 arm of the ER stress in tumor-associated dendritic cells. These recent findings uncover a new immunoregulatory role for ER stress in the tumor microenvironment and suggest that targeting aberrant ER stress responses may represent a new strategy to control tumor-induced immunosuppression and enhance the effectiveness of emerging immunotherapies. Citation Format: Juan R. Cubillos-Ruiz. ER stress responses as new immune checkpoints in cancer [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr IA07.