Therapeutic strategies to reverse immunosuppressive breast cancer microenvironment

Abstract

Breast cancer is one of the most commonly diagnosed cancers in women and is also the leading cause of death. Metastatic and recurrent breast cancer is associated with poor prognosis. Despite advanced multidisciplinary approaches in breast cancer treatment, there are still many therapeutic failures resulting in recurrence, metastasis, and death. Researchers have postulated that an appropriate microenvironment is needed for the growth of the tumor cells. As a result, there has been increased interest in developing innovative therapies targeting the microenvironment. Although chemotherapy is capable of inducing cytotoxic T cell infiltration within the tumor microenvironment, the efficacy of the antitumor immune responses may be limited by the development of immunosuppressive networks. Improved understanding of immune tumor promoting and antitumor mediators in breast cancer has created new opportunities for targeted therapies. Immunotherapy with immune checkpoint inhibitors is beginning to show promise for breast cancer. Adoptive T cell therapy remains an active research area in patients with breast cancer. This review summarizes the current knowledge of immune breast cancer microenvironment and outlines the innovative therapeutic regimens, including T cell based immunotherapy and combination regimens with immune checkpoint inhibitors, which are under clinical investigation.

Macrophage Polarization: Anti-Cancer Strategies to Target Tumor-Associated Macrophage in Breast Cancer

“…Table enlisted ongoing clinical trials clinically investigated agents targeting TAMs. Pexidartinib, another CSF1R inhibitor, is still under study in clinical trials phase Ib/II with Eribulin against metastatic triple‐negative breast cancer patient [Tamkus and Joginpally, ]. These studies indicate that M‐CSF or CSF1 are effective candidates against the tumor therapies directing to inhibit macrophage recruitment [DeNardo et al, ; Swartz et al, ].…”

Recent Discoveries of Macromolecule- and Cell-Based Biomarkers and Therapeutic Implications in Breast Cancer

“…Ipilimumab, an anti-CTLA-4 monoclonal antibody, was the first immune checkpoint inhibitor approved by the FDA in March 2011 for the treatment of metastatic melanoma. Subsequently, several other immune checkpoint inhibitors, such as the CTLA-4 inhibitor, tremelimumab, and antibodies against PD-1, nivolumab, and pembrolizumab have been approved by the FDA for treating advanced solid tumors [ 232 ]. Several phase I clinical trials examining immune checkpoint inhibitors in advanced breast cancer are promising.…”

“…Despite these differences, TNBC is consistently associated with better outcomes compared with other subtypes when treated with immunotherapy, as TNBC has a higher PD-L1 expression. In addition, TNBC is correlated with higher TIL infiltration, which can promote an immune response [ 232 ].…”

“…Chemotherapy and radiotherapy can overcome this problem by inducing specific antitumor immune responses by inducing immunogenic tumor cell death. Consequently, combination strategies of immunotherapy and chemotherapy/radiotherapy are being extensively evaluated in prospective clinical trials, mostly for immune checkpoint blockade [ 232 ].…”

“…For adoptive T cell therapy, a phase II study (NCT01147016) to evaluate the safety and efficacy of the combination of neoadjuvant chemotherapy and HER2Bi armed anti-CD3 activated T cells is being conducted [ 232 ].…”