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Towards Immunotherapy-Induced Normalization of the Tumor Microenvironment

Immunotherapies modulate the function of immune cells to eradicate cancer cells through various mechanisms. These therapies are successful across a spectrum of cancers, but they are curative only in a subset of patients. Indeed, a major obstacle to the success of immunotherapies is the immunosuppres...

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Autores principales: Melo, Vinicio, Bremer, Edwin, Martin, John D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9196132/
https://www.ncbi.nlm.nih.gov/pubmed/35712656
http://dx.doi.org/10.3389/fcell.2022.908389
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author Melo, Vinicio
Bremer, Edwin
Martin, John D.
author_facet Melo, Vinicio
Bremer, Edwin
Martin, John D.
author_sort Melo, Vinicio
collection PubMed
description Immunotherapies modulate the function of immune cells to eradicate cancer cells through various mechanisms. These therapies are successful across a spectrum of cancers, but they are curative only in a subset of patients. Indeed, a major obstacle to the success of immunotherapies is the immunosuppressive nature of the tumor microenvironment (TME), comprising the stromal component and immune infiltrate of tumors. Importantly, the TME in most solid cancers is characterized by sparsely perfused blood vessels resulting from so-called pathological angiogenesis. In brief, dysregulated development of new vessels results in leaky tumor blood vessels that inefficiently deliver oxygen and other nutrients. Moreover, the occurrence of dysregulated fibrosis around the lesion, known as pathological desmoplasia, further compresses tumor blood vessels and impairs blood flow. TME normalization is a clinically tested treatment strategy to reverse these tumor blood vessel abnormalities resulting in stimulated antitumor immunity and enhanced immunotherapy efficacy. TME normalization includes vascular normalization to reduce vessel leakiness and reprogramming of cancer-associated fibroblast to decompress vessels. How immunotherapies themselves normalize the TME is poorly understood. In this review, we summarize current concepts and progress in TME normalization. Then, we review observations of immunotherapy-induced TME normalization and discuss the considerations for combining vascular normalizing and immunotherapies. If TME could be more completely normalized, immunotherapies could be more effective in more patients.
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spelling pubmed-91961322022-06-15 Towards Immunotherapy-Induced Normalization of the Tumor Microenvironment Melo, Vinicio Bremer, Edwin Martin, John D. Front Cell Dev Biol Cell and Developmental Biology Immunotherapies modulate the function of immune cells to eradicate cancer cells through various mechanisms. These therapies are successful across a spectrum of cancers, but they are curative only in a subset of patients. Indeed, a major obstacle to the success of immunotherapies is the immunosuppressive nature of the tumor microenvironment (TME), comprising the stromal component and immune infiltrate of tumors. Importantly, the TME in most solid cancers is characterized by sparsely perfused blood vessels resulting from so-called pathological angiogenesis. In brief, dysregulated development of new vessels results in leaky tumor blood vessels that inefficiently deliver oxygen and other nutrients. Moreover, the occurrence of dysregulated fibrosis around the lesion, known as pathological desmoplasia, further compresses tumor blood vessels and impairs blood flow. TME normalization is a clinically tested treatment strategy to reverse these tumor blood vessel abnormalities resulting in stimulated antitumor immunity and enhanced immunotherapy efficacy. TME normalization includes vascular normalization to reduce vessel leakiness and reprogramming of cancer-associated fibroblast to decompress vessels. How immunotherapies themselves normalize the TME is poorly understood. In this review, we summarize current concepts and progress in TME normalization. Then, we review observations of immunotherapy-induced TME normalization and discuss the considerations for combining vascular normalizing and immunotherapies. If TME could be more completely normalized, immunotherapies could be more effective in more patients. Frontiers Media S.A. 2022-05-30 /pmc/articles/PMC9196132/ /pubmed/35712656 http://dx.doi.org/10.3389/fcell.2022.908389 Text en Copyright © 2022 Melo, Bremer and Martin. https://creativecommons.org/licenses/by/4.0/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) and the copyright owner(s) 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.
spellingShingle Cell and Developmental Biology
Melo, Vinicio
Bremer, Edwin
Martin, John D.
Towards Immunotherapy-Induced Normalization of the Tumor Microenvironment
title Towards Immunotherapy-Induced Normalization of the Tumor Microenvironment
title_full Towards Immunotherapy-Induced Normalization of the Tumor Microenvironment
title_fullStr Towards Immunotherapy-Induced Normalization of the Tumor Microenvironment
title_full_unstemmed Towards Immunotherapy-Induced Normalization of the Tumor Microenvironment
title_short Towards Immunotherapy-Induced Normalization of the Tumor Microenvironment
title_sort towards immunotherapy-induced normalization of the tumor microenvironment
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9196132/
https://www.ncbi.nlm.nih.gov/pubmed/35712656
http://dx.doi.org/10.3389/fcell.2022.908389
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