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REVIEW article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1513421
This article is part of the Research Topic Deciphering Cell-Cell Interactions in Triple-Negative Breast Cancer View all articles

Patterns of immune evasion in triple-negative breast cancer and new potential therapeutic targets: a review

Provisionally accepted
Lucía Serrano García Lucía Serrano García Beatriz Jávega Beatriz Jávega Antonio Llombart-Cussac Antonio Llombart-Cussac María Gión María Gión José Manuel Pérez-García José Manuel Pérez-García Javier Cortés Javier Cortés Leonor Fernández-Murga Leonor Fernández-Murga *
  • Spanish Breast Cancer Group, Madrid, Madrid, Spain

The final, formatted version of the article will be published soon.

    Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by the absence of progesterone and estrogen receptors and low (or absent) HER2 expression. TNBC accounts for 15-20% of all breast cancers. It is associated with younger age, a higher mutational burden, and an increased risk of recurrence and mortality. Standard treatment for TNBC primarily relies on cytotoxic agents, such as taxanes, anthracyclines, and platinum compounds for both early and advanced stages of the disease. Several targeted therapies, including bevacizumab and sunitinib, have failed to demonstrate significant clinical benefit in TNBC. The emergence of immune checkpoint inhibitors (ICI) has revolutionized cancer treatment. By stimulating the immune system, ICIs induce a durable anti-tumor response across various solid tumors. TNBC is a particularly promising target for treatment with ICIs due to the higher levels of tumor-infiltrating lymphocytes (TIL), increased PD-L1 expression, and higher mutational burden, which generates tumor-specific neoantigens that activate immune cells. ICIs administered as monotherapy in advanced TNBC yields only a modest response; however, response rates significantly improve when ICIs are combined with cytotoxic agents, particularly in tumors expressing PD-L1. Pembrolizumab is approved for use in both early and advanced TNBC in combination with standard chemotherapy. However, more research is needed to identify more potent biomarkers, and to better elucidate the synergism of ICIs with other targeted agents. In this review, we explore the challenges of immunotherapy in TNBC, examining the mechanisms of tumor progression mediated by immune cells within the tumor microenvironment, and the signaling pathways involved in both primary and acquired resistance. Finally, we provide a comprehensive overview of ongoing clinical trials underway to investigate novel immune-targeted therapies for TNBC.

    Keywords: Triple negative breast cancer, Immunosuppression, Immunotherapy, Therapeutic target, signaling pathway, Tumor Microenvironment

    Received: 18 Oct 2024; Accepted: 25 Nov 2024.

    Copyright: © 2024 Serrano García, Jávega, Llombart-Cussac, Gión, Pérez-García, Cortés and Fernández-Murga. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Leonor Fernández-Murga, Spanish Breast Cancer Group, Madrid, 28703, Madrid, Spain

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