Immune modulation by ER stress and inflammation in the tumor microenvironment

It is now increasingly evident that the immune system represents a barrier to tumor emergence, growth, and recurrence. Although this idea was originally proposed almost 50 years ago as the immune surveillance hypothesis, it is commonly recognized that, with few rare exceptions, tumor cells always prevail. Thus, one of the central unsolved paradoxes of tumor immunology is how a tumor escapes immune control, which is reflected in the lack of effective autochthonous or vaccine-induced anti-tumor T cell responses. In this review, we discuss the role of the endoplasmic reticulum (ER) stress response/unfolded protein response (UPR) in the immunomodulation of myeloid cells and T cells. Specifically, we will discuss how the tumor cell UPR polarizes myeloid cells in a cell-extrinsic manner, and how in turn, thus polarized myeloid cells negatively affect T cell activation and clonal expansion. (C) 2015 Elsevier Ireland Ltd. All rights reserved.