title: Immune modulation by ER stress and inflammation in the tumor microenvironment.
abstract: 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.
authors.affiliation: The Laboratory of Immunology, Department of Medicine and Moores Cancer Center, University of California, 9500 Gilman Drive, La Jolla, San Diego, CA 92093-0815.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Rodvold
authors.affiliation: The Laboratory of Immunology, Department of Medicine and Moores Cancer Center, University of California, 9500 Gilman Drive, La Jolla, San Diego, CA 92093-0815.
authors.forename: Navin R
authors.initials: NR
authors.lastname: Mahadevan
authors.affiliation: The Laboratory of Immunology, Department of Medicine and Moores Cancer Center, University of California, 9500 Gilman Drive, La Jolla, San Diego, CA 92093-0815. Electronic address: mzanetti@ucsd.edu.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Zanetti
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D017951:Antigen Presentation; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D059865:Endoplasmic Reticulum Stress; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D019139:Tumor Escape; D059016:Tumor Microenvironment; D056811:Unfolded Protein Response
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators
keywords: Cell-nonautonomous; Inflammation; Myeloid cells; T cells; Tumor microenvironment; Unfolded protein response