Combination Immunotherapy Strategies in Breast Cancer

Abstract

Purpose of Review We summarize combination immunotherapy strategies for the treatment of breast cancer, with a focus on metastatic disease. First, a general overview of combination approaches is presented according to breast cancer subtype. Second, additional review of promising combination approaches is presented. Recent Findings Combination strategies utilizing chemotherapy or radiotherapy with immune checkpoint inhibition are being evaluated across multiple phase III trials. Dual immunotherapy strategies, such as dual immune checkpoint inhibition or combined co-stimulation/co-inhibition, have supportive preclinical evidence and are under early clinical investigation. Modulation of the immune microenvironment via cytokines and vaccination strategies, as well as locally focused treatments to enhance antigenic responses, are active areas of research. Summary Pre-clinical and translational research sheds new light on numerous ways the immune system may be modulated to fight against cancer. We describe current and emerging combination approaches which may improve patient outcomes in metastatic breast cancer.

Endocrine therapy for the treatment of leptomeningeal carcinomatosis in luminal breast cancer: a comprehensive review

“…Immunotherapy is also another emerging field that might bring hope to patients with LMD. It seems that CNS metastasis responds to these agents independent of PDL1 status, and even if immunotherapy seems more suitable for the TN BC subtype, targeted agents such as CDK4/6 and mTOR/AKT/PI3K inhibitors seem to alter immunogenicity in HR+ patients, thus opening further possibilities, such as combining trials of target agents with immunotherapy or sequential therapies of these agents [ 84 , 85 ].…”

Activation of cytotoxic T lymphocytes by self-differentiated myeloid-derived dendritic cells for killing breast cancer cells expressing folate receptor alpha protein

“…Immune regulation in the TME was also reported as a prognosis for BC [ 52 ], suggesting vital role of TME in BC treatment. At present, the use of immune checkpoint inhibitors, such as anti-programmed death-ligand 1 (PD-L1) and anti-cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) antibodies, in combination with standard treatments, such as chemotherapy and radiotherapy, is being evaluated in clinical trials with promising results [ 53 ]. Chemotherapy and radiotherapy help to optimize BC antigen presentation, which facilitates a proper anti-tumor immune response [ 54 ].…”

Endogenous and Therapeutic Estrogens: Maestro Conductors of the Microenvironment of ER+ Breast Cancers

“…Strategies to overcome the immunosuppressed microenvironment and increase CD8+ T cell infiltration, as for other immunologically "cold" cancers, are critical. Robust interest supports development of approaches to modulate functional states and/or manipulate recruitment of immune cells, such as macrophages, natural killer cells and γδ T cells, (reviewed in [61,72,94,124,150,[263][264][265][266]). Beyond specific immune cell targets, modulation of other features and cell types in the ER+ TME such as the vasculature, CAFs, and properties of the extracellular matrix (reviewed in [124,149,150]), will address the interactive relationships among all of the components of the environment.…”