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  2. JAML promotes the antitumor role of tumor-resident CD8+ T cells by facilitating their innate-like function in human lung cancer

JAML promotes the antitumor role of tumor-resident CD8+ T cells by facilitating their innate-like function in human lung cancer

  • Cancer Lett. 2024 May 28:590:216839. doi: 10.1016/j.canlet.2024.216839.
Zhixing Hao 1 Zhongwei Xin 1 Yongyuan Chen 1 Zheyu Shao 1 Wei Lin 2 Wenxuan Wu 3 Mingjie Lin 1 Qinyuan Liu 1 Di Chen 4 Dang Wu 5 Pin Wu 6
Affiliations

Affiliations

  • 1 Department of Thoracic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310009, China; Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310009, China.
  • 2 Department of Thoracic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310009, China.
  • 3 Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310009, China; Department of Gastrointestinal Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310009, China.
  • 4 Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310009, China; Department of Radiation Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310009, China.
  • 5 Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310009, China; Department of Radiation Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310009, China. Electronic address: wudang@zju.edu.cn.
  • 6 Department of Thoracic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310009, China; Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310009, China. Electronic address: pinwu@zju.edu.cn.
Abstract

Tissue-resident memory CD8+T cells (CD8+TRMs) are thought to play a crucial role in Cancer immunosurveillance. However, the characteristics of CD8+TRMs in the tumor microenvironment (TME) of human non-small cell lung Cancer (NSCLC) remain unclear. Here, we report that CD8+TRMs accumulate explicitly and exhibit a unique gene expression profile in the TME of NSCLC. Interestingly, these tumor-associated CD8+TRMs uniquely exhibit an innate-like phenotype. Importantly, we found that junction adhesion molecule-like (JAML) provides an alternative costimulatory signal to activate tumor-associated CD8+TRMs via combination with Cancer cell-derived CXADR (CXADR Ig-like cell adhesion molecule). Furthermore, we demonstrated that activating JAML could promote the expression of TLR1/2 on CD8+TRMs, inhibit tumor progression and prolong the survival of tumor-bearing mice. Finally, we found that higher CD8+TRMs and JAML expression in the TME could predict favorable clinical outcomes in NSCLC patients. Our study reveals an intrinsic bias of CD8+TRMs for receiving the tumor-derived costimulatory signal in the TME, which sustains their innate-like function and antitumor role. These findings will shed more LIGHT on the biology of CD8+TRMs and aid in the development of potential targeted treatment strategies for NSCLC.

Keywords

Innate-like T cells; Junction adhesion molecule like (JAML); Non-small cell lung cancer (NSCLC); Tissue-resident memory CD8+T cells (CD8+TRMs); Toll-like receptor (TLR).

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