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<p>Host effector CD4<sup>+</sup> T cells emerge as critical mediators for tumor regression but whether they can be activated by adoptively transferred CD8<sup>+</sup> T cells remains unknown. We previously reported that adoptive transfer of interleukin 9 (IL-9)-producing cytotoxic CD8<sup>+</sup> T (Tc9) cells achieved long-term control of tumor growth. Here, we demonstrate that murine tumor-specific Tc9 cells control the outgrowth of antigen-loss relapsed tumors by recruiting and activating host effector CD4<sup>+</sup> T cells. Tc9 cells secreted IL-24 and recruited CCR7-expressing conventional type 2 dendritic cells (cDC2 cells) into tumor-draining lymph nodes to prime host CD4<sup>+</sup> T cells against relapsed tumors. Host CD4<sup>+</sup> T cell or cDC2 deficiency impaired the ability of Tc9 cells to control relapsed tumor outgrowth. Additionally, intratumoral <i>IL24</i> expression correlates with cDC2 and CD4<sup>+</sup> T cell gene signatures in human cancers and their expression is associated with better patient survival. This study reports a mechanism for activation of tumor-specific CD4<sup>+</sup> T cells in vivo.</p>

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Adoptively transferred tumor-specific IL-9-producing cytotoxic CD8+ T cells activate host CD4+ T cells to control tumors with antigen loss

  • 期刊论文

  • 发表日期：

    2025年4月3日

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  • Liuling Xiao,
  • Rui Duan,
  • Wendao Liu,
  • Chuanchao Zhang,
  • Xingzhe Ma,
  • Miao Xian,
  • Qiang Wang,
  • Qi Guo,
  • Wei Xiong,
  • Pan Su,
  • Lingqun Ye,
  • Yabo Li,
  • Ling Zhong,
  • Jianfei Qian,
  • Yong Lu,
  • Zhongming Zhao,
  • Qing Yi

摘要

Host effector CD4+ T cells emerge as critical mediators for tumor regression but whether they can be activated by adoptively transferred CD8+ T cells remains unknown. We previously reported that adoptive transfer of interleukin 9 (IL-9)-producing cytotoxic CD8+ T (Tc9) cells achieved long-term control of tumor growth. Here, we demonstrate that murine tumor-specific Tc9 cells control the outgrowth of antigen-loss relapsed tumors by recruiting and activating host effector CD4+ T cells. Tc9 cells secreted IL-24 and recruited CCR7-expressing conventional type 2 dendritic cells (cDC2 cells) into tumor-draining lymph nodes to prime host CD4+ T cells against relapsed tumors. Host CD4+ T cell or cDC2 deficiency impaired the ability of Tc9 cells to control relapsed tumor outgrowth. Additionally, intratumoral IL24 expression correlates with cDC2 and CD4+ T cell gene signatures in human cancers and their expression is associated with better patient survival. This study reports a mechanism for activation of tumor-specific CD4+ T cells in vivo.