Tumor-Derived IL33 Promotes Tissue-Resident CD8⁺ T Cells and Is Required for Checkpoint Blockade Tumor Immunotherapy.

ABSTRACT: Immune checkpoint blockade (ICB) immunotherapy has revolutionized cancer treatment by prolonging overall survival of patients with cancer. Despite advances in the clinical setting, the immune cellular network in the tumor microenvironment (TME) that mediates such therapy is not well understood. IL33 is highly expressed in normal epithelial cells but downregulated in tumor cells in advanced carcinoma. Here, we showed that IL33 was induced in tumor cells after treatment with ICB such as CTL antigen-4 (CTLA-4) and programmed death-1 (PD-1) mAbs. ST2 signaling in nontumor cells, particularly CD8⁺ T cells, was critical for the antitumor efficacy of ICB immunotherapy. We demonstrated that tumor-derived IL33 was crucial for the antitumor efficacy of checkpoint inhibitors. Mechanistical

SUBMITTER: Chen L 

PROVIDER: S-EPMC7642190 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature