UNI-MB - logo
UMNIK - logo
 
E-resources
Full text
Peer reviewed Open access
  • Autonomous IL-36R signaling...
    Roy, Sumedha; Fitzgerald, Karen; Lalani, Almin; Lai, Chin-Wen; Kim, Aeryon; Kim, Jennie; Ou, Peiqi; Mirsoian, Annie; Liu, Xian; Ramrakhiani, Ambika; Zhao, Huiren; Zhou, Hong; Xu, Haoda; Meisen, Hans; Li, Chi-Ming; Lugt, Bryan Vander; Thibault, Steve; Tinberg, Christine E; DeVoss, Jason; Egen, Jackson; Wu, Lawren C; Noubade, Rajkumar

    The Journal of clinical investigation, 06/2023, Volume: 133, Issue: 12
    Journal Article

    While the rapid advancement of immunotherapies has revolutionized cancer treatment, only a small fraction of patients derive clinical benefit. Eradication of large, established tumors appears to depend on engaging and activating both innate and adaptive immune system components to mount a rigorous and comprehensive immune response. Identifying such agents is a high unmet medical need, because they are sparse in the therapeutic landscape of cancer treatment. Here, we report that IL-36 cytokine can engage both innate and adaptive immunity to remodel an immune-suppressive tumor microenvironment (TME) and mediate potent antitumor immune responses via signaling in host hematopoietic cells. Mechanistically, IL-36 signaling modulates neutrophils in a cell-intrinsic manner to greatly enhance not only their ability to directly kill tumor cells but also promote T and NK cell responses. Thus, while poor prognostic outcomes are typically associated with neutrophil enrichment in the TME, our results highlight the pleiotropic effects of IL-36 and its therapeutic potential to modify tumor-infiltrating neutrophils into potent effector cells and engage both the innate and adaptive immune system to achieve durable antitumor responses in solid tumors.