Harnessing Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer: Opportunities and Barriers to Clinical Integration

Triple-negative breast cancer (TNBC) continues to present a therapeutic challenge due to the fact that by definition, these cancer cells lack the expression of targetable receptors. Current treatment options include cytotoxic chemotherapy, antibody-drug conjugates (ADC), and the PD-1 checkpoint inhibitor, pembrolizumab. Due to high rates of recurrence, current guidelines for early-stage TNBC recommend either multi-agent chemotherapy or chemo-immunotherapy in all patients other than those with node-negative tumors < 0.5 cm. This approach can lead to significant long-term effects for TNBC survivors, driving a growing interest in de-escalating therapy where appropriate. Tumor infiltrating lymphocytes (TILs) represent a promising prognostic and predictive biomarker for TNBC. These diverse immune cells are present in the tumor microenvironment and within the tumor itself, and multiple retrospective studies have demonstrated that a higher number of TILs in early-stage TNBC portends a favorable prognosis. Research has also explored the potential of TIL scores to predict the response to immunotherapy. However, several barriers to the widespread use of TILs in clinical practice remain, including logistical and technical challenges with the scoring of TILs and lack of prospective trials to validate the trends seen in retrospective studies. This review will present the current understanding of the role of TILs in TNBC and discuss the future directions of TIL research.