| Autor: |
Wu, Zi-Xin, Da, Tian-Tian, Huang, Chuan, Wang, Xiao-Qing, Li, Liang, Zhao, Zhi-Bin, Yin, Ting-Ting, Ma, Hai-Qing, Lian, Zhe-Xiong, Long, Jie, Wang, Fei, Cao, Jie |
| Zdroj: |
Cell Communication & Signaling; 12/18/2024, Vol. 22 Issue 1, p1-17, 17p |
| Abstrakt: |
Background: Colorectal cancer (CRC) is one of the most prevalent cancers worldwide. Despite advancements in therapeutic methodologies, it still causes a high rate of patient mortality. CD8+ tissue-resident memory T (TRM) cells are strategically positioned to mediate effective anti-tumor responses. However, the characteristic surface molecules and functions of CD8+ TRM cells exhibit significant heterogeneity. Methods: The roles and anti-tumor biological functions of different CD8+ TRM subsets in CRC were determined by clinical CRC samples, bioinformatics analysis, and in vitro experiments including co-culture experiments and transwell migration assays. The signaling pathways that synergistically regulate the differentiation of CD8+ TRM cells were identified by in vitro CD8+ T cell activation and inhibition assays, and the functioning transcription factors were predicted using the UCSC and JASPAR databases. Results: We found that different CD8+ TRM subsets existed in CRC tumor tissues, which were identified as CD69−CD103−CD8+ TRM, CD69+CD103−CD8+ TRM (SP CD8+ TRM), and CD69+CD103+CD8+ TRM (DP CD8+ TRM) subsets. Compared with SP CD8+ TRM cells, increased infiltration of DP CD8+ TRM cells predicted better prognosis and played a protective role mainly in tumor invasion and lymph node metastasis of CRC. DP CD8+ TRM cells expressed higher levels of effector molecules and exerted stronger anti-tumor effects in a FAS/FASL pathway-dependent manner. Additionally, DP CD8+ TRM cells secreted higher levels of CXCL13 and recruited B cells into tumor tissues through the CXCL13/CXCR5 signaling axis to form tertiary lymphoid structures, participating in anti-tumor immune responses. Notch and TGF-β signaling pathways synergistically regulate the differentiation of DP CD8+ TRM cells. Conclusions: We clarified the roles and mechanisms of different CD8+ TRM subsets in CRC and identified that DP CD8+ TRM cells exert stronger anti-tumor effects and predict better prognosis, which provides ideas for developing new clinically available therapeutic targets. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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