An IL‐33 immunotherapy that blocks tumor growth by establishing innate lymphoid cells. (LB52)

Abstract

An IL‐33 immunotherapy that blocks tumor growth by establishing innate lymphoid cells.Wonyoung Kim1, Juyang Kim1, Hyun Ju Kim2, U‐jeong Moon2, So Yeon Jung2, Hye‐Jeong Choi3, H. R. Cho1,4, B. Kwon1,21Biomedical Research Center, Ulsan University Hospital, School of Medicine, University of Ulsan, Ulsan, Korea2School of Biological Sciences, University of Ulsan, Ulsan, Korea3Department of Pathology, Ulsan University Hospital, School of Medicine, University of Ulsan, Ulsan, Korea4Department of Surgery, Ulsan University Hospital, School of Medicine, University of Ulsan, Ulsan, KoreaAbstract A long‐standing question in the field of tumor immunotherapy is how type 2 T helper cell (Th2) cytokines can block tumor growth. The anti‐tumor effects of Th2 cytokines are particularly prominent when they are manipulated to be continuously secreted in tumor mass. This observation suggests that Th2 cytokines may create a tumor microenvironment unfavorable for tumor growth independently of adaptive immunity. We show here that sustained intratumoral expression of IL‐33 establishes a high numbers of innate lymphoid cells secreting high levels of CXCL1/2 which are induced scenescence of tumor cells. IL‐33 increased intratumoral hypoxia which is induced high levels of CXCR2 and down‐regulation of HIF‐1α in tumor. CXCR2 signaling strongly induces apoptosis of tumor cells, thereby preventing normal angiogenesis in tumor mass. Our results identify a previously unrecognized function of ILC2s which mediate type‐2 innate immunity leading to antitumor activity.$graphic_B005C94A‐61C7‐4E8A‐A3BD‐C0DF9DCCE278$