title: Cell-extrinsic effects of the tumor unfolded protein response on myeloid cells and T cells.
abstract: Tumor-infiltrating myeloid cells, macrophages, and dendritic cells (DCs) are key regulators of tumor immunity and growth. The origin of tumor-derived signals that instruct myeloid cells in the tumor microenvironment is only partially understood. The endoplasmic reticulum (ER) stress response, or unfolded protein response (UPR), provides survival advantages to tumor growth. However, the cell-extrinsic effects of the tumor UPR on immune cells have not been explored. Our laboratory recently showed that the tumor UPR can be transmitted by yet unidentified factor(s) to myeloid cells, macrophages, and DCs. ER stress transmission to receiver myeloid cells upregulates the production of proinflammatory cytokines, and contextually of arginase I, leading to a proinflammatory/suppressive phenotype. DCs imprinted by tumor-borne ER stress transmissible factor(s) have decreased cross-presentation of antigen and defective cross-priming, causing T cell activation without proliferation. When DCs imprinted by transmissible ER stress are admixed with tumor cells and injected in vivo, facilitation of tumor growth is observed. Thus, tumor-borne ER stress plays a hitherto unappreciated role at the tumor/immune interface that ultimately facilitates tumor growth.
authors: The Laboratory of Immunology, Department of Medicine and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA. mzanetti@ucsd.edu
authors: Maurizio
authors: M
authors: Zanetti
mesh_terms: D000818:Animals; D001119:Arginase / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D045142:Cross-Priming / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000166:cytology; D022423:Myeloid Cells / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology*; D059016:Tumor Microenvironment; D056811:Unfolded Protein Response
chemical_list: D016207:Cytokines; D001119:Arginase