title: Tumorigenic and Immunosuppressive Effects of Endoplasmic Reticulum Stress in Cancer.
abstract: Malignant cells utilize diverse strategies that enable them to thrive under adverse conditions while simultaneously inhibiting the development of anti-tumor immune responses. Hostile microenvironmental conditions within tumor masses, such as nutrient deprivation, oxygen limitation, high metabolic demand, and oxidative stress, disturb the protein-folding capacity of the endoplasmic reticulum (ER), thereby provoking a cellular state of "ER stress." Sustained activation of ER stress sensors endows malignant cells with greater tumorigenic, metastatic, and drug-resistant capacity. Additionally, recent studies have uncovered that ER stress responses further impede the development of protective anti-cancer immunity by manipulating the function of myeloid cells in the tumor microenvironment. Here, we discuss the tumorigenic and immunoregulatory effects of ER stress in cancer, and we explore the concept of targeting ER stress responses to enhance the efficacy of standard chemotherapies and evolving cancer immunotherapies in the clinic.
authors.affiliation: Department of Obstetrics and Gynecology, Weill Cornell Medicine, New York, NY 10065, USA; Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY 10065, USA. Electronic address: jur2016@med.cornell.edu.
authors.forename: Juan R
authors.initials: JR
authors.lastname: Cubillos-Ruiz
authors.affiliation: Quentis Therapeutics, Inc., New York, NY 10016, USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Bettigole
authors.affiliation: Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02215, USA; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA. Electronic address: laurie_glimcher@dfci.harvard.edu.
authors.forename: Laurie H
authors.initials: LH
authors.lastname: Glimcher
mesh_terms: D000818:Animals; D059865:Endoplasmic Reticulum Stress; D009362:Neoplasm Metastasis / Q000276:immunology / Q000473:pathology; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology*; D009389:Neovascularization, Pathologic; D019139:Tumor Escape; D059016:Tumor Microenvironment; D056811:Unfolded Protein Response
keywords: ATF6; CHOP; ER stress; IRE1; PERK; UPR; XBP1; cancer; immunotherapy