Abstract
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.