title: Metabolism of L-arginine by myeloid-derived suppressor cells in cancer: mechanisms of T cell suppression and therapeutic perspectives.
abstract: Patients with cancer have an impaired T cell response that can decrease the potential therapeutic benefit of cancer vaccines and other forms of immunotherapy. The establishment of a chronic inflammatory environment in patients with cancer plays a critical role in the induction of T cell dysfunction. The accumulation of myeloid-derived suppressor cells (MDSC) in tumor bearing hosts is a hallmark of malignancy-associated inflammation and a major mediator of the induction of T cell suppression in cancer. Recent findings in tumor bearing mice and cancer patients indicate that the increased metabolism of L-Arginine (L-Arg) by MDSC producing Arginase I inhibits T cell lymphocyte responses. Here, we discuss some of the most recent concepts of how MDSC expressing Arginase I may regulate T cell function in cancer and suggest possible therapeutic interventions to overcome this inhibitory effect.
authors.affiliation: Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center, NewOrleans, Louisiana, USA. praber@lsuhsc.edu
authors.forename: Patrick
authors.initials: P
authors.lastname: Raber
authors.forename: Augusto C
authors.initials: AC
authors.lastname: Ochoa
authors.forename: Paulo C
authors.initials: PC
authors.lastname: Rodríguez
mesh_terms: D000818:Animals; D001119:Arginase / Q000235:genetics / Q000276:immunology*; D001120:Arginine / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007108:Immune Tolerance; D007249:Inflammation / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D023461:Myeloid Progenitor Cells / Q000276:immunology / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
chemical_list: D016207:Cytokines; D009363:Neoplasm Proteins; D001120:Arginine; C574619:ARG1 protein, human; D001119:Arginase