title: Overcoming tumor-mediated immunosuppression.
abstract: Mechanisms of tumor-mediated immunosuppression have been described for several solid and hematological tumors. Tumors inhibit immune responses by attraction of immunosuppressive lymphocytic populations, secretion of immunosuppressive cytokines or expression of surface molecules, which inhibit immune responses by induction of anergy or apoptosis in tumor-infiltrating lymphocytes. This tumor-mediated immunosuppression represents a major obstacle to many immunotherapeutic or conventional therapeutic approaches. In this review we discuss how tumor-mediated immunosuppression interferes with different immunotherapeutic approaches and then give an overview of strategies to overcome it. Particular emphasis is placed on agents or approaches already transferred into clinical settings. Finally the success of immune checkpoint inhibitors targeting CTLA-4 or the PD-1 pathway highlights the enormous therapeutic potential of an effective overcoming of tumor-mediated immunosuppression.
authors.affiliation: Cologne Interventional Immunology, University of Cologne, Cologne, Germany.
authors.forename: Hans Anton
authors.initials: HA
authors.lastname: Schlößer
authors.forename: Sebastian
authors.initials: S
authors.lastname: Theurich
authors.forename: Alexander
authors.initials: A
authors.lastname: Shimabukuro-Vornhagen
authors.forename: Udo
authors.initials: U
authors.lastname: Holtick
authors.forename: Dirk Ludger
authors.initials: DL
authors.lastname: Stippel
authors.forename: Michael
authors.initials: M
authors.lastname: von Bergwelt-Baildon
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology; D060908:CTLA-4 Antigen / Q000378:metabolism; D016207:Cytokines / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007167:Immunotherapy; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D059016:Tumor Microenvironment / Q000276:immunology
chemical_list: D060908:CTLA-4 Antigen; D016207:Cytokines
keywords: CTLA-4; PD-1; PD-L1; cancer; checkpoint inhibitors; immune escape; immunotherapy; tumor-mediated immunosuppression