Role of T cell exhaustion and tissue-resident memory T cells in the expression and prognosis of colorectal cancer
Abstract The tumour microenvironment (TME) is complex and dynamic, and changes significantly with tumour progression. Studying the evolving state of T cells, especially tumour-specific subsets, has become feasible. However, the roles of exhausted T cells (Tex) and pre-exhausted tissue-resident memor...
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| Language: | English |
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Nature Portfolio
2025-08-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-14409-x |
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| author | Han Wu Pei-Wen Fan Ya-Ning Feng Cheng Chang Ting Gui Jia-bei Meng Ruo-Zheng Wang |
| author_facet | Han Wu Pei-Wen Fan Ya-Ning Feng Cheng Chang Ting Gui Jia-bei Meng Ruo-Zheng Wang |
| author_sort | Han Wu |
| collection | DOAJ |
| description | Abstract The tumour microenvironment (TME) is complex and dynamic, and changes significantly with tumour progression. Studying the evolving state of T cells, especially tumour-specific subsets, has become feasible. However, the roles of exhausted T cells (Tex) and pre-exhausted tissue-resident memory T cells (pf-Trm), which emerge after prolonged antigen stimulation, remain unclear. Using single-cell sequencing data, we analyzed the immune landscape of patients with colorectal cancer (CRC) across clinical stages to quantify the abundance of T cell subtypes. Functional enrichment analysis revealed that early stage Tex cells retained some functionality, whereas advanced stage Tex cells showed a significant functional loss. Early stage pf-Trm cells actively participate in immune surveillance and antigen presentation, whereas advanced stage pf-Trm cells exhibit reduced functions. Flow cytometry analysis of clinical cohorts was used to measure the proportions of Tex and pf-Trm. Elevated levels of PD-1 and Tim-3 have been detected in TILs from CRC patients. Data from The Cancer Genome Atlas (TCGA) linked high Tex levels to poor prognosis in CRC, while pf-Trm correlated with better outcomes in early CRC but worse outcomes in advanced CRC due to functional exhaustion. Thus, Tex and pf-Trm cells may serve as prognostic biomarkers, and Tim-3 and CD103 may be promising targets for immune checkpoint inhibitors. |
| format | Article |
| id | doaj-art-7baef1aca6644abd8d4815e0fa2f586c |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-7baef1aca6644abd8d4815e0fa2f586c2025-08-20T04:01:51ZengNature PortfolioScientific Reports2045-23222025-08-0115111610.1038/s41598-025-14409-xRole of T cell exhaustion and tissue-resident memory T cells in the expression and prognosis of colorectal cancerHan Wu0Pei-Wen Fan1Ya-Ning Feng2Cheng Chang3Ting Gui4Jia-bei Meng5Ruo-Zheng Wang6Xinjiang Key Laboratory of Oncology, The Third Affiliated Teaching Hospital (Affiliated Cancer Hospital) of Xinjiang Medical UniversityXinjiang Key Laboratory of Oncology, The Third Affiliated Teaching Hospital (Affiliated Cancer Hospital) of Xinjiang Medical UniversityXinjiang Key Laboratory of Oncology, The Third Affiliated Teaching Hospital (Affiliated Cancer Hospital) of Xinjiang Medical UniversityClinical Key Specialty of Radiotherapy, Health and Welfare CommissionXinjiang Key Laboratory of Oncology, The Third Affiliated Teaching Hospital (Affiliated Cancer Hospital) of Xinjiang Medical UniversityXinjiang Key Laboratory of Oncology, The Third Affiliated Teaching Hospital (Affiliated Cancer Hospital) of Xinjiang Medical UniversityXinjiang Key Laboratory of Oncology, The Third Affiliated Teaching Hospital (Affiliated Cancer Hospital) of Xinjiang Medical UniversityAbstract The tumour microenvironment (TME) is complex and dynamic, and changes significantly with tumour progression. Studying the evolving state of T cells, especially tumour-specific subsets, has become feasible. However, the roles of exhausted T cells (Tex) and pre-exhausted tissue-resident memory T cells (pf-Trm), which emerge after prolonged antigen stimulation, remain unclear. Using single-cell sequencing data, we analyzed the immune landscape of patients with colorectal cancer (CRC) across clinical stages to quantify the abundance of T cell subtypes. Functional enrichment analysis revealed that early stage Tex cells retained some functionality, whereas advanced stage Tex cells showed a significant functional loss. Early stage pf-Trm cells actively participate in immune surveillance and antigen presentation, whereas advanced stage pf-Trm cells exhibit reduced functions. Flow cytometry analysis of clinical cohorts was used to measure the proportions of Tex and pf-Trm. Elevated levels of PD-1 and Tim-3 have been detected in TILs from CRC patients. Data from The Cancer Genome Atlas (TCGA) linked high Tex levels to poor prognosis in CRC, while pf-Trm correlated with better outcomes in early CRC but worse outcomes in advanced CRC due to functional exhaustion. Thus, Tex and pf-Trm cells may serve as prognostic biomarkers, and Tim-3 and CD103 may be promising targets for immune checkpoint inhibitors.https://doi.org/10.1038/s41598-025-14409-xColorectal cancerTumour microenvironmentT-cell exhaustionPre-failure tissue-resident memory T cellsClinical prognosis |
| spellingShingle | Han Wu Pei-Wen Fan Ya-Ning Feng Cheng Chang Ting Gui Jia-bei Meng Ruo-Zheng Wang Role of T cell exhaustion and tissue-resident memory T cells in the expression and prognosis of colorectal cancer Scientific Reports Colorectal cancer Tumour microenvironment T-cell exhaustion Pre-failure tissue-resident memory T cells Clinical prognosis |
| title | Role of T cell exhaustion and tissue-resident memory T cells in the expression and prognosis of colorectal cancer |
| title_full | Role of T cell exhaustion and tissue-resident memory T cells in the expression and prognosis of colorectal cancer |
| title_fullStr | Role of T cell exhaustion and tissue-resident memory T cells in the expression and prognosis of colorectal cancer |
| title_full_unstemmed | Role of T cell exhaustion and tissue-resident memory T cells in the expression and prognosis of colorectal cancer |
| title_short | Role of T cell exhaustion and tissue-resident memory T cells in the expression and prognosis of colorectal cancer |
| title_sort | role of t cell exhaustion and tissue resident memory t cells in the expression and prognosis of colorectal cancer |
| topic | Colorectal cancer Tumour microenvironment T-cell exhaustion Pre-failure tissue-resident memory T cells Clinical prognosis |
| url | https://doi.org/10.1038/s41598-025-14409-x |
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