Frontiers in Immunology (Mar 2024)
Precursor exhausted CD8+T cells in colorectal cancer tissues associated with patient’s survival and immunotherapy responsiveness
- Hao Huang,
- Hao Huang,
- Hao Huang,
- Junwei Ge,
- Junwei Ge,
- Junwei Ge,
- Zhang Fang,
- Zhang Fang,
- Zhang Fang,
- Shaoxian Wu,
- Shaoxian Wu,
- Shaoxian Wu,
- Hongwei Jiang,
- Hongwei Jiang,
- Hongwei Jiang,
- Yanyan Lang,
- Yanyan Lang,
- Yanyan Lang,
- Junjun Chen,
- Junjun Chen,
- Junjun Chen,
- Wenlu Xiao,
- Wenlu Xiao,
- Wenlu Xiao,
- Bin Xu,
- Bin Xu,
- Bin Xu,
- Yingting Liu,
- Yingting Liu,
- Yingting Liu,
- Lujun Chen,
- Lujun Chen,
- Lujun Chen,
- Xiao Zheng,
- Xiao Zheng,
- Xiao Zheng,
- Jingting Jiang,
- Jingting Jiang,
- Jingting Jiang
Affiliations
- Hao Huang
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China
- Hao Huang
- Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China
- Hao Huang
- Institute of Cell Therapy, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China
- Junwei Ge
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China
- Junwei Ge
- Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China
- Junwei Ge
- Institute of Cell Therapy, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China
- Zhang Fang
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China
- Zhang Fang
- Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China
- Zhang Fang
- Institute of Cell Therapy, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China
- Shaoxian Wu
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China
- Shaoxian Wu
- Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China
- Shaoxian Wu
- Institute of Cell Therapy, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China
- Hongwei Jiang
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China
- Hongwei Jiang
- Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China
- Hongwei Jiang
- Institute of Cell Therapy, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China
- Yanyan Lang
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China
- Yanyan Lang
- Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China
- Yanyan Lang
- Institute of Cell Therapy, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China
- Junjun Chen
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China
- Junjun Chen
- Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China
- Junjun Chen
- Institute of Cell Therapy, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China
- Wenlu Xiao
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China
- Wenlu Xiao
- Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China
- Wenlu Xiao
- Institute of Cell Therapy, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China
- Bin Xu
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China
- Bin Xu
- Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China
- Bin Xu
- Institute of Cell Therapy, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China
- Yingting Liu
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China
- Yingting Liu
- Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China
- Yingting Liu
- Institute of Cell Therapy, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China
- Lujun Chen
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China
- Lujun Chen
- Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China
- Lujun Chen
- Institute of Cell Therapy, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China
- Xiao Zheng
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China
- Xiao Zheng
- Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China
- Xiao Zheng
- Institute of Cell Therapy, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China
- Jingting Jiang
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China
- Jingting Jiang
- Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China
- Jingting Jiang
- Institute of Cell Therapy, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China
- DOI
- https://doi.org/10.3389/fimmu.2024.1362140
- Journal volume & issue
-
Vol. 15
Abstract
Exhausted CD8+T cells represent a distinct cellular lineage that emerges during both chronic infections and cancers. Recent studies have shown that persistent antigen exposure can drive the differentiation of precursor exhausted CD8+T cells, termed Tpex cells, which are characterized as TCF-1+PD-1+CD8+T cells. Elevated Tpex cell frequencies in the tumor microenvironment (TME) are associated with improved overall survival (OS) in cancer patients and heightened responsiveness to anti-PD-1 therapy. In our present study, we utilized multi-color immunohistochemistry (mIHC) to determine the localization and clinical implications of tumor-infiltrating Tpex cells within the TME of human colorectal cancer (CRC) tissues. We also conducted a multi-omics integrative analysis using single-cell RNA sequencing (scRNA-seq) data derived from both the murine MC38 tumor model and human CRC tissues. This analysis helped delineate the transcriptional and functional attributes of Tpex cells within the CRC TME. Furthermore, we employed spatial transcriptome sequencing data from CRC patients to investigate the interactions between Tpex cells and other immune cell subsets within the TME. In conclusion, our study not only established a method for Tpex cell detection using mIHC technology but also confirmed that assessing Tpex cells within the CRC TME could be indicative of patients’ survival. We further uncovered the transcriptional and functional characteristics of Tpex cells in the TME and ascertained their pivotal role in the efficacy of immunotherapy against CRC.
Keywords
- precursor exhausted CD8+T cells
- colorectal cancer
- multi-color immunohistochemistry
- multi-omics
- immunotherapy
