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Review
. 2024 Sep 24;16(19):3250.
doi: 10.3390/cancers16193250.

Present and Future of Immunotherapy for Triple-Negative Breast Cancer

Sushmitha Sriramulu  1 , Shivani Thoidingjam  1 , Corey Speers  2   3 , Shyam Nyati  1   4   5
Affiliations
Review

Present and Future of Immunotherapy for Triple-Negative Breast Cancer

Sushmitha Sriramulu et al. Cancers (Basel). .

Abstract

Triple-negative breast cancer (TNBC) lacks the expression of estrogen receptors (ERs), human epidermal growth factor receptor 2 (HER2), and progesterone receptors (PRs). TNBC has the poorest prognosis among breast cancer subtypes and is more likely to respond to immunotherapy due to its higher expression of PD-L1 and a greater percentage of tumor-infiltrating lymphocytes. Immunotherapy has revolutionized TNBC treatment, especially with the FDA's approval of pembrolizumab (Keytruda) combined with chemotherapy for advanced cases, opening new avenues for treating this deadly disease. Although immunotherapy can significantly improve patient outcomes in a subset of patients, achieving the desired response rate for all remains an unmet clinical goal. Strategies that enhance responses to immune checkpoint blockade, including combining immunotherapy with chemotherapy, molecularly targeted therapy, or radiotherapy, may improve response rates and clinical outcomes. In this review, we provide a short background on TNBC and immunotherapy and explore the different types of immunotherapy strategies that are currently being evaluated in TNBC. Additionally, we review why combination strategies may be beneficial, provide an overview of the combination strategies, and discuss the novel immunotherapeutic opportunities that may be approved in the near future for TNBC.

Keywords: TNBC; chemotherapy; immune checkpoint inhibitors; immunotherapy; radiation therapy; triple-negative breast cancer.

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Conflict of interest statement

S.S., S.T., S.N.: no COIs; C.S.: Exact Sciences (paid consultant—no direct conflict).

Figures

Figure 1
Figure 1
Immunological components of TNBC tumor microenvironment. This illustration sets forth the immunological components of the TNBC tumor microenvironment, which includes tumor-infiltrating lymphocytes (TILs), regulatory T cells (Tregs), tumor-associated macrophages (TAMs), cancer-associated fibroblasts (CAFs), tumor-associated neutrophils (TANs), dendritic cells (DCs), natural killer (NK) cells, myeloid-derived suppressor cells (MDSCs), cancer-associated adipocytes (CAAs), and immune checkpoints.
Figure 2
Figure 2
Current clinical immunotherapy approaches in TNBC. Clinical immunotherapy approaches for TNBC have been diversified in recent years and this illustration summarizes those strategies which include cytokines, mAbs/ADCs, immune checkpoint inhibitors, vaccines, adoptive cell therapies, and oncolytic virus therapy.
Figure 3
Figure 3
Mechanism of action of ICIs targeting PD-L1, PD-1, and CTLA-4. T-cell inactivation and the prevention of tumor cell death are caused by their binding to the corresponding ligands on the surface of cancer cells. Immune checkpoint inhibition promotes anticancer activity and promotes T-cell activation.
See this image and copyright information in PMC

References

    1. Zagami P., Carey L.A. Triple negative breast cancer: Pitfalls and progress. NPJ Breast Cancer. 2022;8:95. doi: 10.1038/s41523-022-00468-0. - DOI - PMC - PubMed
    1. Bauer K.R., Brown M., Cress R.D., Parise C.A., Caggiano V. Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: A population-based study from the California cancer Registry. Cancer. 2007;109:1721–1728. doi: 10.1002/cncr.22618. - DOI - PubMed
    1. Loizides S., Constantinidou A. Triple negative breast cancer: Immunogenicity, tumor microenvironment, and immunotherapy. Front. Genet. 2022;13:1095839. doi: 10.3389/fgene.2022.1095839. - DOI - PMC - PubMed
    1. Liedtke C., Mazouni C., Hess K.R., Andre F., Tordai A., Mejia J.A., Symmans W.F., Gonzalez-Angulo A.M., Hennessy B., Green M., et al. Response to Neoadjuvant Therapy and Long-Term Survival in Patients with Triple-Negative Breast Cancer. J. Clin. Oncol. 2023;41:1809–1815. doi: 10.1200/JCO.22.02572. - DOI - PubMed
    1. Blows F.M., Driver K.E., Schmidt M.K., Broeks A., van Leeuwen F.E., Wesseling J., Cheang M.C., Gelmon K., Nielsen T.O., Blomqvist C., et al. Subtyping of breast cancer by immunohistochemistry to investigate a relationship between subtype and short and long term survival: A collaborative analysis of data for 10,159 cases from 12 studies. PLoS Med. 2010;7:e1000279. doi: 10.1371/journal.pmed.1000279. - DOI - PMC - PubMed

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