Endoplasmic Reticulum Stress Responses in Intratumoral Immune Cells: Implications for Cancer Immunotherapy

Protective anti-tumor immune responses are mediated by effector molecules that enable successful elimination of malignant cells. As the site where transmembrane and secreted proteins are generated, the endoplasmic reticulum (ER) of immune cells plays a key role in this process. Recent studies have indicated that adverse conditions within tumors perturb ER homeostasis in infiltrating immune cells, which can impede the development of effective anticancer immunity. Here, we describe how the tumor microenvironment induces ER stress in immune cells, and discuss the detrimental consequences of persistent ER stress responses in intratumoral immune populations. We also explore the concept of targeting ER stress responses to reinvigorate endogenous anti-tumor immunity and enhance the efficacy of various forms of cancer immunotherapy.