The prognostic significance of TILs as a biomarker in triple-negative breast cancer: what is the role of TILs in TME of TNBC?

Abstract

Triple-negative breast cancer (TNBC) accounts for approximately 15-20% of all breast cancers, and its poor response to treatment has been a major problem in the field of breast cancer. In recent years, the application of immune checkpoint inhibitors has introduced a new era of treatment. The IMpassion 130 trial used PD-L1 as a mature biomarker for immunotherapy in metastatic TNBC, but the population screened, which was only patients with positive PD-L1 expression, was too narrow. Otherwise, it could not be determined whether the PD-L1-positive group benefited from immunotherapy in early TNBC, but this was confirmed in the KEYNOTE-522 and IMpassion 031 studies, in which there was no significant difference in the benefit, whether patients were PD-L1-positive or not. Therefore, how to screen more suitable biomarkers for accurate immunotherapy has become a burning and persistent problem to be solved. In fact, immune infiltration has always been our focus in the process of exploring immunotherapy in TNBC, and tumor infiltrating lymphocytes (TILs) have been well-known for decades as a prognostic factor in early TNBC. Furthermore, TILs are positively correlated with both patient survival and pathological complete response (pCR) after neoadjuvant chemotherapy. Recently, increasingly more foundational experiments and clinical trial verifications suggest that TILs could contain more biomarkers. Thus, in this review, we will assess the composition and heterogeneity of TILs, their evaluation standards, their relationship with TNBC prognosis and the prediction ability of different treatment options in TNBC, and their correlation with other biomarkers in the clinical application. We also summarize new studies that show the future potential of TILs.