Prognostic significance of CD8+tumor-infiltrating lymphocytes in operable breast cancer: a meta-analysis

Background As key mediators of antitumor immunity, CD8 + tumor-infiltrating lymphocytes present antigens and initiate robust immune responses against cancer cells. When stratified by location, CD8 + T lymphocytes were counted and classified as intratumoral, stromal, or total CD8 + tumor-infiltrating lymphocytes. Despite their crucial role, the impact, especially the specific type of CD8 + T lymphocytes on breast cancer prognosis remains controversial. This meta-analysis synthesized evidence to delineate the relationship between CD8 + tumor-infiltrating lymphocytes density of different counting methods and breast cancer patient outcomes. Methods PubMed, Embase, and the Cochrane Library were systemically searched from inception through January 2024 for studies evaluating the prognostic significance of CD8 + tumor-infiltrating lymphocytes in breast cancer. The primary endpoint was disease-free survival (DFS), and the second endpoints were overall survival (OS), breast cancer-specific survival (BCSS), and recurrence-free survival (RFS). Results Thirty-four studies encompassing 23,626 breast cancer patients were included. Pooled hazard ratios (HRs) indicated a significant association of high CD8 + TIL presence with improved DFS (HR = 0.63; 95% CI = 0.54-0.73), OS (HR = 0.72; 95% CI = 0.65-0.79), BCSS (HR = 0.67; 95% CI = 0.58-0.78), and RFS (HR = 0.53; 95% CI = 0.38-0.73). Stratification by TIL location (intratumoral [iCD8], stromal [sCD8], or total [tCD8]) did not significantly impact DFS or OS. Conclusion High CD8 + TIL density in breast cancer patients is correlated with a favorable prognosis, irrespective of the location of CD8 + tumor-infiltrating lymphocytes. These findings affirm the prognostic utility of CD8 + TIL assessment and may guide future immunotherapeutic strategies.