Adoptively Transferred Tumor-Specific Il-9-Producing Cytotoxic CD8+ T Cells Activate Host CD4+ T Cells to Control Tumors With Antigen Loss

Authors

• 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

Language

English

Publication Date

4-1-2025

Journal

Nature Cancer

DOI

10.1038/s43018-025-00935-0

PMID

40181089

PMCID

PMC13470645

PubMedCentral® Posted Date

8-14-2026

PubMedCentral® Full Text Version

Author MSS

Abstract

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.

Keywords

Animals, CD4-Positive T-Lymphocytes, Mice, CD8-Positive T-Lymphocytes, Interleukins, Humans, Lymphocyte Activation, Adoptive Transfer, Dendritic Cells, Mice, Inbred C57BL, T-Lymphocytes, Cytotoxic, Antigens, Neoplasm, Immunotherapy, Adoptive, Cell Line, Tumor, Neoplasms, Interleukin-24

Published Open-Access

yes

Recommended Citation

Xiao, Liuling; Duan, Rui; Liu, Wendao; et al., "Adoptively Transferred Tumor-Specific Il-9-Producing Cytotoxic CD8+ T Cells Activate Host CD4+ T Cells to Control Tumors With Antigen Loss" (2025). Faculty, Staff and Student Publications. 1025.
https://digitalcommons.library.tmc.edu/uthshis_docs/1025