Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer: Prognostic Significance, Predictive Value, and Emerging Directions for Clinical Implementation

Triple-negative breast cancer (TNBC) represents a biologically aggressive subtype with limited therapeutic targets; however, tumor-infiltrating lymphocytes (TILs) have emerged as the most robust immune biomarker with compelling prognostic and predictive significance. This comprehensive review synthesizes current evidence on TIL assessment methodology; the immunobiological landscape of TNBC, including regulatory T cell populations and PD-L1 correlations; gene expression underpinnings of the tumor immune microenvironment; and systematic evidence from meta-analyses and clinical trials. Meta-analytic estimates demonstrate that high TIL levels are associated with improved overall survival (HR 0.58, 95% CI 0.48-0.71) and disease-free survival (HR 0.66, 95% CI 0.57-0.76), with each 10% TIL increment conferring incremental benefit. High TILs predict superior pathologic complete response to neoadjuvant chemotherapy (OR 2.14, 95% CI 1.43-3.19), with lymphocyte-predominant breast cancer achieving pCR rates exceeding 80% with pembrolizumab-based chemoimmunotherapy. Future directions include prospective TIL-guided treatment trials, artificial intelligence-enabled standardization, and emerging adoptive TIL cellular therapies for metastatic disease.