Tumor-Infiltrating Lymphocytes and Immune Response in HER2-Positive Breast Cancer

Simple Summary It has been known for decades that the immune system plays an important role in the etiology of breast cancer. Also, lymph node spread is the most important prognostic factor in breast cancer, and the presence of tumor-infiltrating lymphocytes (TILs) predicts a beneficial anti-HER2 therapeutic response. The latest translational clinical research aims to strengthen a patient's immune system to tackle and kill cancer cells more effectively. However, immune system cells can either establish a protective antitumor response or, conversely, induce chronic inflammation that promotes disease progression. This ambivalence depends, to a large extent, on the immune cell infiltrate present in the tumor and the communication that these cells establish with the tumor cells. This review aims to summarize the current knowledge of the immune system-breast cancer relationship, emphasizing TILs and their importance as biomarkers of clinical progression of the disease. Human epidermal growth factor receptor 2-positive (HER2-positive) breast cancer accounts for 15 to 25% of breast cancer cases. Although therapies based on the use of monoclonal anti-HER2 antibodies present clinical benefit for a subtype of patients with HER2-positive breast cancer, more than 50% of them are unresponsive to targeted therapies or they eventually relapse. In recent years, reactivation of the adaptive immune system in patients with solid tumors has emerged as a therapeutic option with great potential for clinical benefit. Since the approval of the first treatment directed against HER2 as a therapeutic target, the range of clinical options has expanded greatly, and, in this sense, cellular immunotherapy with T cells relies on the cytotoxicity generated by these cells, which ultimately leads to antitumor activity. Lymphocytic infiltration of tumors encompasses a heterogeneous population of immune cells within the tumor microenvironment that exhibits distinct patterns of immune activation and exhaustion. The prevalence and prognostic value of tumor-infiltrating lymphocyte (TIL) counts are associated with a favorable prognosis in HER2-positive breast cancers. This review discusses emerging findings that contribute to a better understanding of the role of immune infiltrates in HER2-positive breast cancer. In addition, it summarizes the most recent results in HER2-positive breast cancer immunotherapy and anticipates which therapeutic strategies could be applied in the immediate future.