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 journalArticle

1 Citation (Scopus)

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

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Interleukin-10
Dendritic Cells
Apoptosis
T-Lymphocytes
Neoplasms
Immunosuppressive Agents
Cellular Immunity
Tumor-Infiltrating Lymphocytes
Proteins
Immunotherapy
Half-Life
Cytokines

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Cite this

Targeting Tumors with IL-10 Prevents Dendritic Cell-Mediated CD8+ T Cell Apoptosis. / Qiao, Jian; Liu, Zhida; Dong, Chunbo; Luan, Yan; Zhang, Anli; Moore, Casey; Fu, Kai; Peng, Jianjian; Wang, Yang; Ren, Zhenhua; Han, Chuanhui; Xu, Ting; Fu, Yang-Xin.

In: Cancer Cell, Vol. 35, No. 6, 10.06.2019, p. 901-915.e4.

Research output: Contribution to journalArticle

Qiao, J, Liu, Z, Dong, C, Luan, Y, Zhang, A, Moore, C, Fu, K, Peng, J, Wang, Y, Ren, Z, Han, C, Xu, T & Fu, Y-X 2019, 'Targeting Tumors with IL-10 Prevents Dendritic Cell-Mediated CD8+ T Cell Apoptosis', Cancer Cell, vol. 35, no. 6, pp. 901-915.e4. https://doi.org/10.1016/j.ccell.2019.05.005
Qiao, Jian ; Liu, Zhida ; Dong, Chunbo ; Luan, Yan ; Zhang, Anli ; Moore, Casey ; Fu, Kai ; Peng, Jianjian ; Wang, Yang ; Ren, Zhenhua ; Han, Chuanhui ; Xu, Ting ; Fu, Yang-Xin. / Targeting Tumors with IL-10 Prevents Dendritic Cell-Mediated CD8+ T Cell Apoptosis. In: Cancer Cell. 2019 ; Vol. 35, No. 6. pp. 901-915.e4.
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