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Co-expression of PD-1 with TIGIT or PD-1 with TIM-3 on tumor-infiltrating CD8+ T cells showed synergistic effects on improved disease-free survival in treatment-naïve CRC patients.
- Source :
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International Immunopharmacology . Jun2023, Vol. 119, pN.PAG-N.PAG. 1p. - Publication Year :
- 2023
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Abstract
- • Tumor-infiltrating lymphocytes are key players in predicting prognoses of cancer patients. • High levels of PD1+ with TIGIT+ or PD-1+ with TIM-3+ CD8+ TILs are associated with improved DFS. • Combination of immune checkpoints on CD8+ TILs are more sensitive predictive biomarkers in CRC patients than single ones. Immune checkpoints (ICs) are highly expressed on tumor-infiltrating immune cells (TIICs) in different malignancies, including colorectal cancer (CRC). T cells play crucial roles in shaping CRC, and their presence in the tumor microenvironment (TME) has proven to be one of the best predictors of clinical outcomes. A crucial component of the immune system is cytotoxic CD8+ T cells (CTLs), which play decisive roles in the prognosis of CRC. In this study, we investigated associations of immune checkpoints expressed on tumor-infiltrating CD8+ T cells with disease-free survival (DFS) in 45 naïve-treatment CRC patients. First, we examined the associations of single ICs, and found that CRC patients with higher levels of T-cell immunoglobulin and ITIM-domain (TIGIT), T-cell immunoglobulin and mucin domain-3 (TIM-3) and programmed cell death-1 (PD-1) CD8+ T cells tended to have longer DFS. Interestingly, when PD-1 expression was combined with other ICs, there were more evident and stronger associations between higher levels of PD-1+ with TIGIT+ or PD-1+ with TIM-3+ tumor-infiltrating CD8+ T cells and longer DFS. Our findings for TIGIT were validated in The Cancer Genome Atlas (TCGA) CRC dataset. This study is the first to report on the association of co-expression of PD-1 with TIGIT and PD-1 with TIM-3 in CD8+ T cells and improved DFS in treatment-naïve CRC patients. This work highlights the significance of immune checkpoint expression on tumor-infiltrating CD8+ T cells as critical predictive biomarkers, especially when co-expression of different ICs is considered. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15675769
- Volume :
- 119
- Database :
- Academic Search Index
- Journal :
- International Immunopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 163944453
- Full Text :
- https://doi.org/10.1016/j.intimp.2023.110207