Roles of Tumor-Infiltrating Lymphocytes and Antitumor Immune Responses as Predictive and Prognostic Markers in...

Tumor-infiltrating lymphocytes (TILs) are thought to play important roles in tumor shrinkage and survival prolongation in patients with breast cancer receiving neoadjuvant chemotherapy (NAC). TILs are mononuclear immune cells such as lymphocytes and plasma cells, including CD4+ and CD8+ T cells, natural killer cells, B cells, macrophages, regulatory T cells (Tregs), and myeloid/dendritic cells. The pre-NAC presence of more T cells and fewer Tregs in biopsy samples of primary breast tumors is known to contribute to tumor shrinkage and prolonged survival. This review was conducted to elucidate these roles in patients with breast cancer treated with NAC. Publications selected for inclusion in this review were identified by a PubMed search for articles published in English, performed using the terms "breast cancer", "neoadjuvant chemotherapy", "tumor-infiltrating lymphocyte", "pathological complete response", and "immune response". The search was completed in July 2024. The functional roles of TILs in the achievement of these outcomes may vary by tumor subtype; increases and decreases in TIL levels before and after NAC have been shown to have conflicting effects. Biomarkers have been reported to predict local responses in the tumor microenvironment (e.g., immune-related gene signatures) and systemic immune responses (e.g., neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios). Immune gene signatures and immune cell infiltration do not appear to be universally associated with tumor response or outcome in patients with breast cancer treated with NAC. The functional roles of TILs in breast tumor response and breast cancer survival may vary by tumor subtype, and conflicting results for the same subtypes may be due to differences in NAC regimens, immune responses, tumor heterogeneity, sample size, and the technical methods used to evaluate TILs in tumor samples.