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Breast Cancer Tumor Microenvironment and Molecular Aberrations Hijack Tumoricidal Immunity

SIMPLE SUMMARY: Immune therapy is designed to stimulate tumoricidal effects in a variety of solid tumors including breast carcinomas. However, the emergence of resistant clones leads to treatment failure. Understanding the molecular, cellular, and microenvironmental aberrations is crucial to uncover...

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Autores principales: Lin, Huey-Jen, Liu, Yingguang, Lofland, Denene, Lin, Jiayuh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8774102/
https://www.ncbi.nlm.nih.gov/pubmed/35053449
http://dx.doi.org/10.3390/cancers14020285
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author Lin, Huey-Jen
Liu, Yingguang
Lofland, Denene
Lin, Jiayuh
author_facet Lin, Huey-Jen
Liu, Yingguang
Lofland, Denene
Lin, Jiayuh
author_sort Lin, Huey-Jen
collection PubMed
description SIMPLE SUMMARY: Immune therapy is designed to stimulate tumoricidal effects in a variety of solid tumors including breast carcinomas. However, the emergence of resistant clones leads to treatment failure. Understanding the molecular, cellular, and microenvironmental aberrations is crucial to uncovering underlying mechanisms and developing advanced strategies for preventing or combating these resistant malignancies. This review will summarize research findings revealing various mechanisms employed to hijack innate and adaptive immune surveillance mechanisms, develop hypoxic and tumor promoting metabolism, and foster an immune tolerance microenvironment. In addition, it will highlight potential targets for therapeutic approaches. ABSTRACT: Breast cancer is the most common malignancy among females in western countries, where women have an overall lifetime risk of >10% for developing invasive breast carcinomas. It is not a single disease but is composed of distinct subtypes associated with different clinical outcomes and is highly heterogeneous in both the molecular and clinical aspects. Although tumor initiation is largely driven by acquired genetic alterations, recent data suggest microenvironment-mediated immune evasion may play an important role in neoplastic progression. Beyond surgical resection, radiation, and chemotherapy, additional therapeutic options include hormonal deactivation, targeted-signaling pathway treatment, DNA repair inhibition, and aberrant epigenetic reversion. Yet, the fatality rate of metastatic breast cancer remains unacceptably high, largely due to treatment resistance and metastases to brain, lung, or bone marrow where tumor bed penetration of therapeutic agents is limited. Recent studies indicate the development of immune-oncological therapy could potentially eradicate this devastating malignancy. Evidence suggests tumors express immunogenic neoantigens but the immunity towards these antigens is frequently muted. Established tumors exhibit immunological tolerance. This tolerance reflects a process of immune suppression elicited by the tumor, and it represents a critical obstacle towards successful antitumor immunotherapy. In general, immune evasive mechanisms adapted by breast cancer encompasses down-regulation of antigen presentations or recognition, lack of immune effector cells, obstruction of anti-tumor immune cell maturation, accumulation of immunosuppressive cells, production of inhibitory cytokines, chemokines or ligands/receptors, and up-regulation of immune checkpoint modulators. Together with altered metabolism and hypoxic conditions, they constitute a permissive tumor microenvironment. This article intends to discern representative incidents and to provide potential innovative therapeutic regimens to reinstate tumoricidal immunity.
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spelling pubmed-87741022022-01-21 Breast Cancer Tumor Microenvironment and Molecular Aberrations Hijack Tumoricidal Immunity Lin, Huey-Jen Liu, Yingguang Lofland, Denene Lin, Jiayuh Cancers (Basel) Review SIMPLE SUMMARY: Immune therapy is designed to stimulate tumoricidal effects in a variety of solid tumors including breast carcinomas. However, the emergence of resistant clones leads to treatment failure. Understanding the molecular, cellular, and microenvironmental aberrations is crucial to uncovering underlying mechanisms and developing advanced strategies for preventing or combating these resistant malignancies. This review will summarize research findings revealing various mechanisms employed to hijack innate and adaptive immune surveillance mechanisms, develop hypoxic and tumor promoting metabolism, and foster an immune tolerance microenvironment. In addition, it will highlight potential targets for therapeutic approaches. ABSTRACT: Breast cancer is the most common malignancy among females in western countries, where women have an overall lifetime risk of >10% for developing invasive breast carcinomas. It is not a single disease but is composed of distinct subtypes associated with different clinical outcomes and is highly heterogeneous in both the molecular and clinical aspects. Although tumor initiation is largely driven by acquired genetic alterations, recent data suggest microenvironment-mediated immune evasion may play an important role in neoplastic progression. Beyond surgical resection, radiation, and chemotherapy, additional therapeutic options include hormonal deactivation, targeted-signaling pathway treatment, DNA repair inhibition, and aberrant epigenetic reversion. Yet, the fatality rate of metastatic breast cancer remains unacceptably high, largely due to treatment resistance and metastases to brain, lung, or bone marrow where tumor bed penetration of therapeutic agents is limited. Recent studies indicate the development of immune-oncological therapy could potentially eradicate this devastating malignancy. Evidence suggests tumors express immunogenic neoantigens but the immunity towards these antigens is frequently muted. Established tumors exhibit immunological tolerance. This tolerance reflects a process of immune suppression elicited by the tumor, and it represents a critical obstacle towards successful antitumor immunotherapy. In general, immune evasive mechanisms adapted by breast cancer encompasses down-regulation of antigen presentations or recognition, lack of immune effector cells, obstruction of anti-tumor immune cell maturation, accumulation of immunosuppressive cells, production of inhibitory cytokines, chemokines or ligands/receptors, and up-regulation of immune checkpoint modulators. Together with altered metabolism and hypoxic conditions, they constitute a permissive tumor microenvironment. This article intends to discern representative incidents and to provide potential innovative therapeutic regimens to reinstate tumoricidal immunity. MDPI 2022-01-07 /pmc/articles/PMC8774102/ /pubmed/35053449 http://dx.doi.org/10.3390/cancers14020285 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Lin, Huey-Jen
Liu, Yingguang
Lofland, Denene
Lin, Jiayuh
Breast Cancer Tumor Microenvironment and Molecular Aberrations Hijack Tumoricidal Immunity
title Breast Cancer Tumor Microenvironment and Molecular Aberrations Hijack Tumoricidal Immunity
title_full Breast Cancer Tumor Microenvironment and Molecular Aberrations Hijack Tumoricidal Immunity
title_fullStr Breast Cancer Tumor Microenvironment and Molecular Aberrations Hijack Tumoricidal Immunity
title_full_unstemmed Breast Cancer Tumor Microenvironment and Molecular Aberrations Hijack Tumoricidal Immunity
title_short Breast Cancer Tumor Microenvironment and Molecular Aberrations Hijack Tumoricidal Immunity
title_sort breast cancer tumor microenvironment and molecular aberrations hijack tumoricidal immunity
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8774102/
https://www.ncbi.nlm.nih.gov/pubmed/35053449
http://dx.doi.org/10.3390/cancers14020285
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