Journal Article
. 2020 May; 11:634.
doi: 10.3389/fimmu.2020.00634.

IL36 Cooperates With Anti-CTLA-4 mAbs to Facilitate Antitumor Immune Responses

Qiuxia Qu 1 Zhiwei Zhai 1 Jieni Xu 2 Song Li 2 Cheng Chen 1 Binfeng Lu 1 
Affiliations
  • PMID: 32351508
  •     51 References
  •     7 citations

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.

Keywords: CTLA-4; IL36; immunotherapy; mAb; treg.

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