AUTHOR=Huang Hao , Ge Junwei , Fang Zhang , Wu Shaoxian , Jiang Hongwei , Lang Yanyan , Chen Junjun , Xiao Wenlu , Xu Bin , Liu Yingting , Chen Lujun , Zheng Xiao , Jiang Jingting 

TITLE=Precursor exhausted CD8+T cells in colorectal cancer tissues associated with patient’s survival and immunotherapy responsiveness

JOURNAL=Frontiers in Immunology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1362140

DOI=10.3389/fimmu.2024.1362140

ISSN=1664-3224

ABSTRACT=<p>Exhausted CD8<sup>+</sup>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<sup>+</sup>T cells, termed T<sub>pex</sub> cells, which are characterized as TCF-1<sup>+</sup>PD-1<sup>+</sup>CD8<sup>+</sup>T cells. Elevated T<sub>pex</sub> 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 T<sub>pex</sub> 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 T<sub>pex</sub> cells within the CRC TME. Furthermore, we employed spatial transcriptome sequencing data from CRC patients to investigate the interactions between T<sub>pex</sub> cells and other immune cell subsets within the TME. In conclusion, our study not only established a method for T<sub>pex</sub> cell detection using mIHC technology but also confirmed that assessing T<sub>pex</sub> cells within the CRC TME could be indicative of patients’ survival. We further uncovered the transcriptional and functional characteristics of T<sub>pex</sub> cells in the TME and ascertained their pivotal role in the efficacy of immunotherapy against CRC.</p>