2. Academic Validation
  3. Distribution, phenotype, functional and clinical relevance of CD8+CD103+ tissue-resident memory T cells in human gastric cancer

Distribution, phenotype, functional and clinical relevance of CD8+CD103+ tissue-resident memory T cells in human gastric cancer

  • Cancer Immunol Immunother. 2022 Jul;71(7):1645-1654. doi: 10.1007/s00262-021-03105-0.
Yang Shen  # 1 2,  Xiao-Long Li  # 3,  Yu-Xian Li 1,  Zhi-Guo Shan 4,  Yong-Liang Zhao 4,  Ping Cheng 1,  Zhuo Zhao 1,  Jin-Yu Zhang 1,  Weisan Chen 5,  Yuan Zhuang 1,  Dai-Yuan Ma 2,  Quan-Ming Zou 1,  Yuan Qiu 6,  Liu-Sheng Peng 7
Affiliations

Affiliations

  • 1 National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, 400038, China.
  • 2 Department of Oncology, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, Sichuan Province, China.
  • 3 Department of General Surgery of Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China.
  • 4 Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
  • 5 La Trobe Institute for Molecular Science, School of Molecular Science, La Trobe University, Bundoora, VIC, 3085, Australia.
  • 6 Department of General Surgery of Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China. xiaoq2037@qq.com.
  • 7 National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, 400038, China. pengliusheng06@163.com.
  • # Contributed equally.
PMID: 34767045 DOI: 10.1007/s00262-021-03105-0
Abstract

CD8+CD103+ tissue-resident memory T cells (TRMs) are involved in tumor immune response and linked to favorable clinical outcome in human Cancer. However, the distribution, phenotype, functional properties and clinical relevance of these cells in gastric Cancer (GC) remain elusive. Here, our data show that, in comparison to non-tumor tissues, the percentages of CD8+CD103+ TRMs in tumors are significantly decreased. Most tumor-infiltrating CD8+CD103+ TRMs are CD45RA-CCR7- effector-memory cells with higher PD-1 and 4-1BB expression than those from non-tumor tissues. Further, tumor-infiltrating CD8+CD103+ TRMs show impaired cytolytic capacity due to decreased granzyme B and perforin expression. Moreover, ex vivo PD-1 blockade could restore the cytolytic capacity of tumor-infiltrating CD8+CD103+ TRMs, and such anti-PD-1-mediated reinvigoration of CD8+CD103+ TRMs could be further enhanced by 4-1BB co-stimulation. Finally, lower levels of Tumor-infiltrating CD8+CD103+ TRMs are positively correlated with GC progression and poor patients' survival. Our data suggest that restoring CD8+CD103+ TRM function by combining PD-1 blockade and 4-1BB co-stimulation may be a promising strategy for treating GC.

Keywords

4-1BB; CD8+CD103+ tissue-resident memory T cells; Gastric cancer; PD-1.

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