title: Targeting iNOS to increase efficacy of immunotherapies.
abstract: Inducible NO synthase (iNOS/NOS2) protein expression is a well-studied predictor of poor outcome in multiple cancers, and it has also been associated with inflammatory and immunosuppressive processes in the tumor microenvironment. Immunotherapies are becoming increasingly key components in cancer treatment, and iNOS is receiving more attention as a potential regulator of treatment resistance. As we have reported in pancreatic cancer, by modulation of effector T-cell activity, iNOS overexpression may allow the tumor to escape the immune response through creating a microenvironment which causes recalcitrance to immunotherapy. Based on studies describing its role in the immune environment of multiple cancers, strategies that include iNOS inhibitors as combination partners may enhance immunotherapy approaches. The expression and the function of iNOS both depend on the tumor type and microenvironment, as well as on the patient's treatment history. Thus, enhancing immunotherapies, including adoptive T-cell therapies and checkpoint blockade, will require tailored cancer-specific approaches and additional levels of microenvironment regulation.
authors.affiliation: a Department of Melanoma Medical Oncology , The University of Texas MD Anderson Cancer Center , Houston , TX , USA.
authors.forename: Suhendan
authors.initials: S
authors.lastname: Ekmekcioglu
authors.affiliation: a Department of Melanoma Medical Oncology , The University of Texas MD Anderson Cancer Center , Houston , TX , USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Grimm
authors.affiliation: a Department of Melanoma Medical Oncology , The University of Texas MD Anderson Cancer Center , Houston , TX , USA.|b Department of Genomic Medicine , The University of Texas MD Anderson Cancer Center , Houston , TX , USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Roszik
mesh_terms: D006801:Humans; D007165:Immunosuppression Therapy; D007167:Immunotherapy / Q000379:methods*; D016219:Immunotherapy, Adoptive; D009369:Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000628:therapy*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology; D059016:Tumor Microenvironment / Q000276:immunology
chemical_list: C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II
keywords: cancer; combination therapies; iNOS/NOS2; immunosuppression; immunotherapy