@ARTICLE{10.3389/fimmu.2020.00634, AUTHOR={Qu, Qiuxia and Zhai, Zhiwei and Xu, Jieni and Li, Song and Chen, Cheng and Lu, Binfeng}, TITLE={IL36 Cooperates With Anti-CTLA-4 mAbs to Facilitate Antitumor Immune Responses}, JOURNAL={Frontiers in Immunology}, VOLUME={11}, YEAR={2020}, URL={https://www.frontiersin.org/articles/10.3389/fimmu.2020.00634}, DOI={10.3389/fimmu.2020.00634}, ISSN={1664-3224}, ABSTRACT={Despite the great impact on long-term survival of some cancer patients, the immune checkpoint blockade (ICB) therapy is limited by its low response rates for most cancers. There is a pressing need for novel combination immunotherapies that overcome the resistance to current ICB therapies. Cytokines play a pivotal role in tumor immunotherapy by helping initiating and driving antitumor immune responses. Here, we demonstrated that, besides conventional CD4+ and CD8+ T cells, IL36 surprisingly increased the number of tumor-infiltrating regulatory T (Treg) cells in vivo and enhanced proliferation of Tregs in vitro. Administration of CTLA-4 monoclonal antibodies (mAbs) strongly enhanced IL36-stimulated antitumor activities through depletion of Tregs. In addition, a cancer gene therapy using the IL36-loaded nanoparticles in combination with CTLA-4 mAbs additively reduced lung metastasis of breast tumor cells. We further showed that the combined therapy of CTLA-4 mAbs and IL36 led to an increase in proliferation and IFN-γ production by CD4+ and CD8+ T cells when compared to single therapy with CTLA-4 mAbs or IL36. Collectively, our findings demonstrated a new combination therapy that could improve the clinical response to ICB immunotherapy for cancer.} }