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      Targeting the interleukin-17 immune axis for cancer immunotherapy

      review-article
      Author(s): ,
      Publication date (Electronic):
      Journal: The Journal of Experimental Medicine
      Publisher: Rockefeller University Press

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          Abstract

          IL-17 plays versatile roles during tumorigenesis. Here, Vitiello and Miller summarize current knowledge in harnessing IL-17–producing γδ and Th17 cells for successful cancer immunotherapy.

          Abstract

          The role of IL-17 in cancer remains controversial. Emerging evidence suggests that during early oncogenesis IL-17 supports tumor growth, whereas in established tumors IL-17 production by γδ and Th17 cells potentiates antitumor immunity. Consequently, γδ and Th17 cells are attractive targets for immunotherapy in the IL-17 immune axis. To optimize IL-17–based immunotherapy, a deeper understanding of the cytokines dictating IL-17 production and the polarity of γδ and Th17 cells is critical. Here, we delve into the dichotomous roles of IL-17 in cancer and provide insight into the tumor microenvironment conducive for successful IL-17–based γδ and Th17 cell immunotherapy.

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          Most cited references126

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          Nivolumab versus Docetaxel in Advanced Nonsquamous Non–Small-Cell Lung Cancer

          Hossein Borghaei, Luis Paz-Ares, Leora Horn … (2015)
          Nivolumab, a fully human IgG4 programmed death 1 (PD-1) immune-checkpoint-inhibitor antibody, disrupts PD-1-mediated signaling and may restore antitumor immunity.
          Article 0 comments Cited 2128 times – based on 0 reviews     Review now
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            Improved Survival with Ipilimumab in Patients with Metastatic Melanoma

            F. Stephen Hodi, Steven J O'Day, David F McDermott … (2010)
            An improvement in overall survival among patients with metastatic melanoma has been an elusive goal. In this phase 3 study, ipilimumab--which blocks cytotoxic T-lymphocyte-associated antigen 4 to potentiate an antitumor T-cell response--administered with or without a glycoprotein 100 (gp100) peptide vaccine was compared with gp100 alone in patients with previously treated metastatic melanoma. A total of 676 HLA-A*0201-positive patients with unresectable stage III or IV melanoma, whose disease had progressed while they were receiving therapy for metastatic disease, were randomly assigned, in a 3:1:1 ratio, to receive ipilimumab plus gp100 (403 patients), ipilimumab alone (137), or gp100 alone (136). Ipilimumab, at a dose of 3 mg per kilogram of body weight, was administered with or without gp100 every 3 weeks for up to four treatments (induction). Eligible patients could receive reinduction therapy. The primary end point was overall survival. The median overall survival was 10.0 months among patients receiving ipilimumab plus gp100, as compared with 6.4 months among patients receiving gp100 alone (hazard ratio for death, 0.68; P<0.001). The median overall survival with ipilimumab alone was 10.1 months (hazard ratio for death in the comparison with gp100 alone, 0.66; P=0.003). No difference in overall survival was detected between the ipilimumab groups (hazard ratio with ipilimumab plus gp100, 1.04; P=0.76). Grade 3 or 4 immune-related adverse events occurred in 10 to 15% of patients treated with ipilimumab and in 3% treated with gp100 alone. There were 14 deaths related to the study drugs (2.1%), and 7 were associated with immune-related adverse events. Ipilimumab, with or without a gp100 peptide vaccine, as compared with gp100 alone, improved overall survival in patients with previously treated metastatic melanoma. Adverse events can be severe, long-lasting, or both, but most are reversible with appropriate treatment. (Funded by Medarex and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00094653.)
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              Nivolumab versus Docetaxel in Advanced Squamous-Cell Non–Small-Cell Lung Cancer

              Julie Brahmer, Karen L. Reckamp, Paul Baas … (2015)
              New England Journal of Medicine, 373(2), 123-135
              Article 0 comments Cited 1761 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Exp Med
                Journal ID (iso-abbrev): J. Exp. Med
                Journal ID (publisher-id): jem
                Journal ID (hwp): jem
                Title: The Journal of Experimental Medicine
                Publisher: Rockefeller University Press
                ISSN (Print): 0022-1007
                ISSN (Electronic): 1540-9538
                Publication date Collection: 06 January 2020
                Publication date (Electronic): 14 November 2020
                Volume: 217
                Issue: 1
                Electronic Location Identifier: e20190456
                Affiliations
                [1]S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, New York, NY
                Author notes
                Correspondence to George Miller: george.miller@ 123456nyulangone.org
                Author information
                https://orcid.org/0000-0001-8482-4100
                Article
                Publisher ID: 20190456
                DOI: 10.1084/jem.20190456
                PMC ID: 7037254
                PubMed ID: 31727783
                SO-VID: e044ef6e-f52f-4fac-94d0-a64dfca00c23
                Copyright © © 2019 Vitiello and Miller
                License:

                This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).

                History
                Date received : 19 July 2019
                Date revision received : 23 August 2019
                Date accepted : 08 October 2019
                Page count
                Pages: 11
                Funding
                Funded by: National Institutes of Health, DOI https://doi.org/10.13039/100000002;
                Award ID: CA168611
                Award ID: CA203105
                Award ID: CA215471
                Award ID: CA19311
                Award ID: DK106025
                Funded by: National Institutes of Health, DOI https://doi.org/10.13039/100000002;
                Award ID: L30 TR002111
                Categories
                Subject: Reviews
                Subject: Review
                Subject: 322
                Subject: 314
                Series title: Cytokines Focus

                ScienceOpen disciplines: Medicine
                Data availability:
                ScienceOpen disciplines: Medicine

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