title: Exploiting IL-17-producing CD4+ and CD8+ T cells to improve cancer immunotherapy in the clinic.
abstract: Cancer immunotherapy is one the most effective approaches for treating patients with tumors, as it bolsters the generation and persistence of memory T cells. In preclinical work, it has been reported that adoptively transferred CD4+ and CD8+ lymphocytes that secrete IL-17A (i.e., Th17 and Tc17 cells) regress tumors to a greater extent than IFN-γ(+)Th1 or Tc1 cells in vivo. Herein, we review the mechanisms underlying how infused Th17 and Tc17 cells regress established malignancies in clinically relevant mouse models of cancer. We also discuss how unique signaling cues--such as co-stimulatory molecules (ICOS and 41BB), cytokines (IL-12 and IL-23) or pharmaceutical reagents (Akt inhibitors, etc.)--can be exploited to bolster the therapeutic potential of IL-17(+) lymphocytes with an emphasis on using this knowledge to improve next-generation clinical trials for patients with cancer.
authors.affiliation: Department of Microbiology and Immunology, Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, HO612C, Charleston, SC, 29425, USA.|Department of Surgery, Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC, USA.|Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences - WULS, Nowoursynowska 159, 02-776, Warsaw, Poland.
authors.forename: Kinga
authors.initials: K
authors.lastname: Majchrzak
authors.affiliation: Department of Microbiology and Immunology, Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, HO612C, Charleston, SC, 29425, USA.|Department of Surgery, Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC, USA.
authors.forename: Michelle H
authors.initials: MH
authors.lastname: Nelson
authors.affiliation: Department of Microbiology and Immunology, Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, HO612C, Charleston, SC, 29425, USA.|Department of Surgery, Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC, USA.
authors.forename: Stefanie R
authors.initials: SR
authors.lastname: Bailey
authors.affiliation: Department of Microbiology and Immunology, Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, HO612C, Charleston, SC, 29425, USA.|Department of Surgery, Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC, USA.
authors.forename: Jacob S
authors.initials: JS
authors.lastname: Bowers
authors.affiliation: Department of Microbiology and Immunology, Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, HO612C, Charleston, SC, 29425, USA.
authors.forename: Xue-Zhong
authors.initials: XZ
authors.lastname: Yu
authors.affiliation: Department of Surgery, Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC, USA.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Rubinstein
authors.affiliation: Department of Chemistry and Biochemistry, College of Charleston, 202 Calhoun Street, Charleston, SC, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Himes
authors.affiliation: Department of Microbiology and Immunology, Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, HO612C, Charleston, SC, 29425, USA. paulos@musc.edu.|Department of Surgery, Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC, USA. paulos@musc.edu.
authors.forename: Chrystal M
authors.initials: CM
authors.lastname: Paulos
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D007167:Immunotherapy; D060889:Inducible T-Cell Co-Stimulator Protein / Q000502:physiology; D018664:Interleukin-12 / Q000502:physiology; D020381:Interleukin-17 / Q000096:biosynthesis*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology / Q000502:physiology
chemical_list: C556692:ICOS protein, human; C508717:IL17A protein, human; D060889:Inducible T-Cell Co-Stimulator Protein; D020381:Interleukin-17; D018664:Interleukin-12
keywords: ACT; Cancer; Immunotherapy; Tc17; Th17
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