Cellular Immune Responses and Immune Escape Mechanisms in Breast Cancer: Determinants of Immunotherapy

Abstract

More recently, immunotherapy has emerged as a novel potentially effective therapeutic option also for solid malignancies such as breast cancer (BC). Relevant approaches, however, are determined by the 2 main elements of cancer immunoediting - the elimination of nascent transformed cells by immunosurveillance on the one hand and tumor immune escape on the other hand. Correspondingly, we here review the role of the various cellular immune players within the host-protective system and dissect the mechanisms of immune evasion leading to tumor progression. If the immune balance of disseminated BC cell dormancy (equilibrium phase) is lost, distant metastatic relapse may occur. The relevant cellular antitumor responses and translational immunotherapeutic options will also be discussed in terms of clinical benefit and future directions in BC management.

Keywords: Breast cancer; Cellular immunity; Immune escape; Immunoediting; Immunosurveillance; Immunotherapy.

Fig. 1

Adoptive immunotherapy (ADI) of metastasized breast cancer patients. Process of ADI treatment preparation (PB = Peripheral blood; BM = bone marrow; DC = dendritic cell; TC = T cell; MCF-7 = human breast cancer cell line MCF-7; TA = tumor antigen). Adapted from [36,57].

Fig. 2

Checkpoint inhibitors (CTLA-4 = Cytotoxic T-lymphocyte-associated antigen 4; PD-(L)1 = programmed cell death protein (ligand) 1; APC = antigen-presenting cell; MDSC = myeloid-derived suppressor cell; ROS = reactive oxygen species; TCR = T cell receptor; MEDI 4736/MPDL 3280A = anti-PD-L1 monoclonal antibodies). Adapted from [54].