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

Abstract

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.

Keywords: HER2-positive breast cancer; immunotherapy; tumor-infiltrating lymphocytes.

Figure 1

The predominant contribution of the different lymphocytic infiltrates to either tumor suppression or progression, including NK cells, cytotoxic T cells, T helper (Th) cell subsets, regulatory T (Treg) cells, B cells, and tumor-associated macrophages, comprising those with antitumorigenic (M1) or protumorigenic (M2) properties. Through the secretion of different factors, these immune populations play key roles in shaping the microenvironment, thereby driving either immune-mediated anti- or protumor activity. (Created with BioRender.com, accessed on 17 January 2022).