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CD5 Expression Dynamically Changes During the Differentiation of Human CD8+ T Cells Predicting Clinical Response to Immunotherapy

  • Young Ju Kim (Medical Research Center for Combinatorial Tumor Immunotherapy, Department of Microbiology and Immunology, Chonnam National University Medical School) ;
  • Kyung Na Rho (Medical Research Center for Combinatorial Tumor Immunotherapy, Department of Microbiology and Immunology, Chonnam National University Medical School) ;
  • Saei Jeong (Medical Research Center for Combinatorial Tumor Immunotherapy, Department of Microbiology and Immunology, Chonnam National University Medical School) ;
  • Gil-Woo Lee (Medical Research Center for Combinatorial Tumor Immunotherapy, Department of Microbiology and Immunology, Chonnam National University Medical School) ;
  • Hee-Ok Kim (Selecxine) ;
  • Hyun-Ju Cho (Department of Internal Medicine, Chonnam National University Hwasun Hospital) ;
  • Woo Kyun Bae (Department of Internal Medicine, Chonnam National University Hwasun Hospital) ;
  • In-Jae Oh (Department of Internal Medicine, Chonnam National University Hwasun Hospital) ;
  • Sung-Woo Lee (Medical Research Center for Combinatorial Tumor Immunotherapy, Department of Microbiology and Immunology, Chonnam National University Medical School) ;
  • Jae-Ho Cho (Medical Research Center for Combinatorial Tumor Immunotherapy, Department of Microbiology and Immunology, Chonnam National University Medical School)
  • Received : 2023.06.30
  • Accepted : 2023.08.16
  • Published : 2023.08.31
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Abstract

Defining the molecular dynamics associated with T cell differentiation enhances our understanding of T cell biology and opens up new possibilities for clinical implications. In this study, we investigated the dynamics of CD5 expression in CD8+ T cell differentiation and explored its potential clinical uses. Using PBMCs from 29 healthy donors, we observed a stepwise decrease in CD5 expression as CD8+ T cells progressed through the differentiation stages. Interestingly, we found that CD5 expression was initially upregulated in response to T cell receptor stimulation, but diminished as the cells underwent proliferation, potentially explaining the differentiation-associated CD5 downregulation. Based on the proliferation-dependent downregulation of CD5, we hypothesized that relative CD5 expression could serve as a marker to distinguish the heterogeneous CD8+ T cell population based on their proliferation history. In support of this, we demonstrated that effector memory CD8+ T cells with higher CD5 expression exhibited phenotypic and functional characteristics resembling less differentiated cells compared to those with lower CD5 expression. Furthermore, in the retrospective analysis of PBMCs from 30 non-small cell lung cancer patients, we found that patients with higher CD5 expression in effector memory T cells displayed CD8+ T cells with a phenotype closer to the less differentiated cells, leading to favorable clinical outcomes in response to immune checkpoint inhibitor (ICI) therapy. These findings highlight the dynamics of CD5 expression as an indicator of CD8+ T cell differentiation status, and have implications for the development of predictive biomarker for ICI therapy.

Keywords

Acknowledgement

We thank JH Rhee (CNU) and DH Yang and IJ Chung (CNUHH) for critical comments on clinical data; HW Ryu, MJ Ryu and SM Ahn (CNU) for laboratory management and administrative assistance; CNU flow cytometric core facilities for assistance with cell sorting; and MS Park (CNUHH) and MS Kim (CNU) for blood collection, mice breeding and care. We also thank the Korean Red Cross and the Biobank of CNU Hwasun Hospital for providing biospecimens used for this study. This work was supported by a grant from the National Research Foundation (NRF) funded by the Korean Ministry of Science and ICT (2020R1A5A2031185, 2020M3A9G3080281 and 2022R1A2C2009385) and by the Korean Ministry of Education (2022R1A6A3A01086438 for SW Lee), a grant (HCRI 19001-1*HCRI20012) of Chonnam National University Hwasun Hospital and a new faculty research grant (2020-2029) of Chonnam National University.

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