title: Intratumorally Establishing Type 2 Innate Lymphoid Cells Blocks Tumor Growth.
abstract: A long-standing question in the field of tumor immunotherapy is how Th2 cytokines block tumor growth. Their antitumor effects are particularly prominent when they are secreted continuously in tumors, suggesting that Th2 cytokines may create a tumor microenvironment unfavorable for tumor growth independently of adaptive immunity. In this study, we show that local production of IL-33 establishes a high number of type 2 innate lymphoid cells (ILC2s) with potent antitumor activity. IL-33 promotes secretion of a massive amount of CXCR2 ligands from ILC2s but creates a tumor microenvironment where tumor cells express CXCR2 through a dysfunctional angiogenesis/hypoxia/reactive oxygen species axis. These two signaling events converge to reinforce tumor cell-specific apoptosis through CXCR2. Our results identify a previously unrecognized antitumor therapeutic pathway wherein ILC2s play a central role.
authors.affiliation: Biomedical Research Center, Ulsan University Hospital and School of Medicine, University of Ulsan, Ulsan 682-714, Republic of Korea;
authors.forename: Juyang
authors.initials: J
authors.lastname: Kim
authors.affiliation: Biomedical Research Center, Ulsan University Hospital and School of Medicine, University of Ulsan, Ulsan 682-714, Republic of Korea;
authors.forename: Wonyoung
authors.initials: W
authors.lastname: Kim
authors.affiliation: School of Biological Sciences, University of Ulsan, Ulsan 680-749, Republic of Korea;
authors.forename: U J
authors.identifier: http://orcid.org/0000-0001-5609-7970
authors.initials: UJ
authors.lastname: Moon
authors.affiliation: School of Biological Sciences, University of Ulsan, Ulsan 680-749, Republic of Korea;
authors.forename: Hyun J
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Pathology, Ulsan University Hospital and School of Medicine, University of Ulsan, Ulsan 682-714, Republic of Korea;
authors.forename: Hye-Jeong
authors.initials: HJ
authors.lastname: Choi
authors.affiliation: Department of Microbiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do 200-701, Republic of Korea;
authors.forename: Jeong-Im
authors.identifier: http://orcid.org/0000-0003-4700-7704
authors.initials: JI
authors.lastname: Sin
authors.affiliation: Biomedical Research Center, Ulsan University Hospital and School of Medicine, University of Ulsan, Ulsan 682-714, Republic of Korea; Department of Internal Medicine, Ulsan University Hospital and School of Medicine, University of Ulsan, Ulsan 682-714, Republic of Korea; and.
authors.forename: Neung H
authors.identifier: http://orcid.org/0000-0002-5648-9189
authors.initials: NH
authors.lastname: Park
authors.affiliation: Biomedical Research Center, Ulsan University Hospital and School of Medicine, University of Ulsan, Ulsan 682-714, Republic of Korea; Department of Surgery, Ulsan University Hospital and School of Medicine, University of Ulsan, Ulsan 682-714, Republic of Korea bkwon@mail.ulsan.ac.kr hrcho@uuh.ulsan.kr.
authors.forename: Hong R
authors.initials: HR
authors.lastname: Cho
authors.affiliation: Biomedical Research Center, Ulsan University Hospital and School of Medicine, University of Ulsan, Ulsan 682-714, Republic of Korea; School of Biological Sciences, University of Ulsan, Ulsan 680-749, Republic of Korea; bkwon@mail.ulsan.ac.kr hrcho@uuh.ulsan.kr.
authors.forename: Byungsuk
authors.identifier: http://orcid.org/0000-0001-8575-0115
authors.initials: B
authors.lastname: Kwon
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D015415:Biomarkers; D045744:Cell Line, Tumor; D054360:Chemokine CXCL1 / Q000378:metabolism; D054426:Chemokine CXCL2 / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D007113:Immunity, Innate; D016130:Immunophenotyping; D000067596:Interleukin-33 / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009369:Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D023063:Receptors, Interleukin-8B / Q000378:metabolism; D015398:Signal Transduction; D047368:Tumor Burden; D059016:Tumor Microenvironment
chemical_list: D000954:Antigens, Surface; D015415:Biomarkers; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D000067596:Interleukin-33; D017382:Reactive Oxygen Species; D023063:Receptors, Interleukin-8B