Patterns of immune evasion in triple-negative breast cancer and new potential therapeutic targets: a review
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 a...
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Frontiers Media S.A.
2024-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1513421/full |
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| author | Lucía Serrano García Beatriz Jávega Antonio Llombart Cussac Antonio Llombart Cussac Antonio Llombart Cussac María Gión José Manuel Pérez-García José Manuel Pérez-García Javier Cortés Javier Cortés Javier Cortés María Leonor Fernández-Murga |
| author_facet | Lucía Serrano García Beatriz Jávega Antonio Llombart Cussac Antonio Llombart Cussac Antonio Llombart Cussac María Gión José Manuel Pérez-García José Manuel Pérez-García Javier Cortés Javier Cortés Javier Cortés María Leonor Fernández-Murga |
| author_sort | Lucía Serrano García |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-ed59e2224298418f99cd7d0c424e01b4 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-ed59e2224298418f99cd7d0c424e01b42024-12-13T05:10:20ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-12-011510.3389/fimmu.2024.15134211513421Patterns of immune evasion in triple-negative breast cancer and new potential therapeutic targets: a reviewLucía Serrano García0Beatriz Jávega1Antonio Llombart Cussac2Antonio Llombart Cussac3Antonio Llombart Cussac4María Gión5José Manuel Pérez-García6José Manuel Pérez-García7Javier Cortés8Javier Cortés9Javier Cortés10María Leonor Fernández-Murga11Medical Oncology Department, Hospital Arnau de Vilanova, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO), Valencia, SpainMedical Oncology Department, Hospital Arnau de Vilanova, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO), Valencia, SpainMedical Oncology Department, Hospital Arnau de Vilanova, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO), Valencia, SpainGrupo Oncología Traslacional, Facultad de Ciencias de la Salud, Universidad Cardenal Herrera-Centro de Estudios Universitarios (CEU), Alfara del Patriarca, SpainMedica Scientia Innovation Research (MEDSIR), Oncoclínicas & Co., Jersey City, NJ, United StatesMedical Oncology Department, Hospital Ramon y Cajal, Madrid, SpainMedica Scientia Innovation Research (MEDSIR), Oncoclínicas & Co., Jersey City, NJ, United StatesInternational Breast Cancer Center (IBCC), Pangaea Oncology, Quiron Group, Barcelona, SpainMedica Scientia Innovation Research (MEDSIR), Oncoclínicas & Co., Jersey City, NJ, United StatesInternational Breast Cancer Center (IBCC), Pangaea Oncology, Quiron Group, Barcelona, SpainUniversidad Europea de Madrid, Faculty of Biomedical and Health Sciences, Department of Medicine, Madrid, SpainMedical Oncology Department, Hospital Arnau de Vilanova, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO), Valencia, SpainTriple-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.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1513421/fulltriple negative breast cancerimmunosuppressionimmunotherapytherapeutic targetsignaling pathwaytumor microenvironment |
| spellingShingle | Lucía Serrano García Beatriz Jávega Antonio Llombart Cussac Antonio Llombart Cussac Antonio Llombart Cussac María Gión José Manuel Pérez-García José Manuel Pérez-García Javier Cortés Javier Cortés Javier Cortés María Leonor Fernández-Murga Patterns of immune evasion in triple-negative breast cancer and new potential therapeutic targets: a review Frontiers in Immunology triple negative breast cancer immunosuppression immunotherapy therapeutic target signaling pathway tumor microenvironment |
| title | Patterns of immune evasion in triple-negative breast cancer and new potential therapeutic targets: a review |
| title_full | Patterns of immune evasion in triple-negative breast cancer and new potential therapeutic targets: a review |
| title_fullStr | Patterns of immune evasion in triple-negative breast cancer and new potential therapeutic targets: a review |
| title_full_unstemmed | Patterns of immune evasion in triple-negative breast cancer and new potential therapeutic targets: a review |
| title_short | Patterns of immune evasion in triple-negative breast cancer and new potential therapeutic targets: a review |
| title_sort | patterns of immune evasion in triple negative breast cancer and new potential therapeutic targets a review |
| topic | triple negative breast cancer immunosuppression immunotherapy therapeutic target signaling pathway tumor microenvironment |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1513421/full |
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