title: Signal transducer and activator of transcription proteins: regulators of myeloid-derived suppressor cell-mediated immunosuppression in cancer.
abstract: The success of cancer immunotherapy in patients depends on overcoming immunosuppressive mechanisms in addition to stimulating effective anticancer immune responses. Myeloid-derived suppressor cells (MDSCs) inhibit a spectrum of immune responses, including adaptive immune responses and innate immune responses at the tumor site. MDSCs have been targeted to overcome immunosuppression either by reducing their numbers or downregulating their immunosuppressive activities. Although signal transducer and activator of transcription (STAT) proteins are recognized as signaling and transcription factors induced by cytokines in normal cells, they also have roles in cancer and cancer-related cells, as well as MDSC differentiation and function. In in vitro and in vivo studies, including studies on humans, selective STAT3 inhibitors such as Stattic and S3I-201 have demonstrated potential in regulating MDSC-mediated immunosuppression. Thus, STAT pathways represent a promising target in cancer immunotherapy. Herein, we review the roles of STAT signaling in MDSC biology, and the clinical potential of STAT inhibitors in regulating tumor-associated immunosuppression mediated by MDSCs.
authors: Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon, 200-701, Republic of Korea.
authors: Hyun-Jeong
authors: HJ
authors: Ko
authors: Laboratory of Microbiology and Immunology, College of Pharmacy, Inje University, Gimhae, 621-749, Republic of Korea. yjeokim@inje.ac.kr.
authors: Yeon-Jeong
authors: YJ
authors: Kim
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects* / Q000276:immunology; D007167:Immunotherapy / Q000379:methods*; D000072737:Myeloid-Derived Suppressor Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D050796:STAT3 Transcription Factor
keywords: Cancer; Immunosuppressive tumor environment; Myeloid-derived suppressor cell; STAT inhibitor; STAT signaling