Targeting Tumors with IL-10 Prevents Dendritic Cell-Mediated CD8+ T Cell Apoptosis

Jian Qiao, Zhida Liu, Chunbo Dong, Yan Luan, Anli Zhang, Casey Moore, Kai Fu, Jianjian Peng, Yang Wang, Zhenhua Ren, Chuanhui Han, Ting Xu, Yang-Xin Fu

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

Increasing evidence demonstrates that interleukin-10 (IL-10), known as an immunosuppressive cytokine, induces antitumor effects depending on CD8+ T cells. However, it remains elusive how immunosuppressive effects of IL-10 contribute to CD8+ T cell-mediated antitumor immunity. We generated Cetuximab-based IL-10 fusion protein (CmAb-(IL10)2) to prolong its half-life and allow tumor-targeted delivery of IL-10. Our results demonstrated potent antitumor effects of CmAb-(IL10)2 with reduced toxicity. Moreover, we revealed a mechanism of CmAb-(IL10)2 preventing dendritic cell (DC)-mediated CD8+ tumor-infiltrating lymphocyte apoptosis through regulating IFN-γ production. When combined with immune checkpoint blockade, CmAb-(IL10)2 significantly improves antitumor effects in mice with advanced tumors. Our findings reveal a DC-regulating role of IL-10 to potentiate CD8+ T cell-mediated antitumor immunity and provide a potential strategy to improve cancer immunotherapy. Qiao et al. generate a Cetuximab-based IL-10 fusion protein for EGFR-targeted delivery of IL-10 to tumors, in which IL-10 regulates IFN-γ production by dendritic cells and enhances CD8+ T cell-dependent antitumor responses. The fusion protein shows high efficacy alone and in combination with anti-PD-L1/CTLA-4.

Original languageEnglish (US)
Pages (from-to)901-915.e4
JournalCancer Cell
Volume35
Issue number6
DOIs
StatePublished - Jun 10 2019

Keywords

  • IL-10
  • TILs
  • apoptosis
  • immunotherapy
  • toxicity
  • tumor targeting

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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