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Review
. 2021 Feb 25:10:600573.
doi: 10.3389/fonc.2020.600573. eCollection 2020.

Immune Checkpoint Inhibitors in Triple Negative Breast Cancer Treatment: Promising Future Prospects

Affiliations
Review

Immune Checkpoint Inhibitors in Triple Negative Breast Cancer Treatment: Promising Future Prospects

Remy Thomas et al. Front Oncol. .

Abstract

Immunotherapy has emerged as the fifth pillar of cancer treatment alongside surgery, radiotherapy, chemotherapy, and targeted therapy. Immune checkpoint inhibitors are the current superheroes of immunotherapy, unleashing a patient's own immune cells to kill tumors and revolutionizing cancer treatment in a variety of cancers. Although breast cancer was historically believed to be immunologically silent, treatment with immune checkpoint inhibitors has been shown to induce modest responses in metastatic breast cancer. Given the inherent heterogeneity of breast tumors, this raised the question whether certain breast tumors might benefit more from immune-based interventions and which cancer cell-intrinsic and/or microenvironmental factors define the likelihood of inducing a potent and durable anti-tumor immune response. In this review, we will focus on triple negative breast cancer as immunogenic breast cancer subtype, and specifically discuss the relevance of tumor mutational burden, the plethora and diversity of tumor infiltrating immune cells in addition to the immunoscore, the presence of immune checkpoint expression, and the microbiome in defining immune checkpoint blockade response. We will highlight the current immune checkpoint inhibitor treatment options, either as monotherapy or in combination with standard-of-care treatment modalities such as chemotherapy and targeted therapy. In addition, we will look into the potential of immunotherapy-based combination strategies using immune checkpoint inhibitors to enhance both innate and adaptive immune responses, or to establish a more immune favorable environment for cancer vaccines. Finally, the review will address the need for unambiguous predictive biomarkers as one of the main challenges of immune checkpoint blockade. To conclude, the potential of immune checkpoint blockade for triple negative breast cancer treatment could be enhanced by exploration of aforementioned factors and treatment strategies thereby providing promising future prospects.

Keywords: combination therapy; immune checkpoint blockade; predictive biomarkers; programmed death ligand-1 (PD-L1); programmed death-1 (PD-1); triple negative breast cancer; tumor infiltrating lymphocytes; tumor mutational burden.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Current Approaches for PD-1 and PD-L1 immune checkpoint inhibition in TNBC. The efficacy of PD-1 and PD-L1 therapy may be hampered due to cancer cell-intrinsic interactions and/or microenvironmental factors along with the expression of immune checkpoint molecules such as PD-L1 that define a potent and durable anti-tumor immune response. Immune checkpoint blockade could be used as monotherapy or in combination with different therapeutic approaches, including chemotherapy, PARP inhibitors with or without VEGFR/CDK/MEK inhibitors, cancer vaccines, and NK cell therapy.

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