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Heterogenous distribution of PD-1+CD39+CD8+ T cell in TME defined its immunotherapeutic biomarker in lung cancer
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  • Jia Zhai,
  • Yao Zhang,
  • Hong Wang,
  • Lei-lei Lv,
  • Yu Shen,
  • Qiu Qu,
  • Cheng Chen
Jia Zhai
First Affiliated Hospital of Soochow University
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Yao Zhang
First Affiliated Hospital of Soochow University
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Hong Wang
First Affiliated Hospital of Soochow University
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Lei-lei Lv
First Affiliated Hospital of Soochow University
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Yu Shen
First Affiliated Hospital of Soochow University
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Qiu Qu
First Affiliated Hospital of Soochow University
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Cheng Chen
First Affiliated Hospital of Soochow University

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Abstract

CD8+ T cells in tumors are heterogenous and exist in multiple differentiation states. Evidence has proposed CD39 as a marker of exhausted and tumor-reactive CD8+ T cells. Here, we analyzed a subset of tumor-infiltrating CD8+ T cells based on the expression of the immunosuppressive ATP ectonucleotidase CD39 and PD-1. Neoplasm-superficial biopsy and intratumoral EBUS-TBNA were used to assess the peripheral and central tumor microenvironment, respectively. CD39+CD8+ T cells dominantly accumulated in the peritumoral compartment of larger tumors and exhibited an exhausted phenotype compatible with PD-1 expression. Compared with CD39+CD8+ T cells, PD-1+CD39+CD8+ T cells are better biomarkers for predicting responses to anti-PD-1 therapy. Collectively, heterogenous distribution may be critical to elicit CD39 expression in lung cancer associated CD8+ T cells. Increased PD-1+CD39+CD8+ T cell levels within the peripheral TME can act as a candidate biomarker for lung cancer immunotherapy.