Tumor-infiltrating lymphocytes, breast cancer subtypes and therapeutic efficacy

Abstract

By analyzing over 2000 samples from a randomized clinical trial, we have recently associated high levels of tumor-infiltrating lymphocytes with an excellent prognosis among triple negative breast cancer patients as well with improved clinical responses to immunogenic chemotherapy among patients bearing HER2 over-expression. These findings suggest that immunomodulation could represent a new approach to treat these aggressive breast cancer subtypes.

Keywords: biomarkers; breast cancer; immunotherapies; prognosis; trastuzumab efficacy; tumor infiltrating lymphocytes.

Figure 1. Possible links between the presence of lymphocytic infiltration at diagnosis and the clinical outcome of breast cancer patients. (A) Tumors that are genetically unstable and/or exhibit high rates of proliferation are associated with high levels of lymphocytic infiltration at diagnosis. (B) Genomic instability facilitates tumor progression as it can help malignant cells to avoid immune recognition by altering their antigenic properties; neoplastic cells establish immunosuppressive mechanisms; T cells are subject to regulation or become exhausted and gradually lose their functions. (C) Chemotherapy can restore functional T cells through high mobility group box 1 (HMGB1)- or myeloid differentiation 88 (MYD88)-mediated signaling cascades; trastuzumab (Trz) can induce functional immune effectors by interacting with Fc receptor-expressing cells such as natural killer cells. Elucidating how tumors that do not present with lymphocytic infiltration at diagnosis avoid immune recognition is critical for the development of efficient therapeutic regimens.