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Dynamic polarization of tumor-associated macrophages and their interaction with intratumoral T cells in an inflamed tumor microenvironment: from mechanistic insights to therapeutic opportunities

Immunotherapy has brought a paradigm shift in the treatment of tumors in recent decades. However, a significant proportion of patients remain unresponsive, largely due to the immunosuppressive tumor microenvironment (TME). Tumor-associated macrophages (TAMs) play crucial roles in shaping the TME by...

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Autores principales: Han, Jiashu, Dong, Luochu, Wu, Mengwei, Ma, Fei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10219223/
https://www.ncbi.nlm.nih.gov/pubmed/37251409
http://dx.doi.org/10.3389/fimmu.2023.1160340
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author Han, Jiashu
Dong, Luochu
Wu, Mengwei
Ma, Fei
author_facet Han, Jiashu
Dong, Luochu
Wu, Mengwei
Ma, Fei
author_sort Han, Jiashu
collection PubMed
description Immunotherapy has brought a paradigm shift in the treatment of tumors in recent decades. However, a significant proportion of patients remain unresponsive, largely due to the immunosuppressive tumor microenvironment (TME). Tumor-associated macrophages (TAMs) play crucial roles in shaping the TME by exhibiting dual identities as both mediators and responders of inflammation. TAMs closely interact with intratumoral T cells, regulating their infiltration, activation, expansion, effector function, and exhaustion through multiple secretory and surface factors. Nevertheless, the heterogeneous and plastic nature of TAMs renders the targeting of any of these factors alone inadequate and poses significant challenges for mechanistic studies and clinical translation of corresponding therapies. In this review, we present a comprehensive summary of the mechanisms by which TAMs dynamically polarize to influence intratumoral T cells, with a focus on their interaction with other TME cells and metabolic competition. For each mechanism, we also discuss relevant therapeutic opportunities, including non-specific and targeted approaches in combination with checkpoint inhibitors and cellular therapies. Our ultimate goal is to develop macrophage-centered therapies that can fine-tune tumor inflammation and empower immunotherapy.
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spelling pubmed-102192232023-05-27 Dynamic polarization of tumor-associated macrophages and their interaction with intratumoral T cells in an inflamed tumor microenvironment: from mechanistic insights to therapeutic opportunities Han, Jiashu Dong, Luochu Wu, Mengwei Ma, Fei Front Immunol Immunology Immunotherapy has brought a paradigm shift in the treatment of tumors in recent decades. However, a significant proportion of patients remain unresponsive, largely due to the immunosuppressive tumor microenvironment (TME). Tumor-associated macrophages (TAMs) play crucial roles in shaping the TME by exhibiting dual identities as both mediators and responders of inflammation. TAMs closely interact with intratumoral T cells, regulating their infiltration, activation, expansion, effector function, and exhaustion through multiple secretory and surface factors. Nevertheless, the heterogeneous and plastic nature of TAMs renders the targeting of any of these factors alone inadequate and poses significant challenges for mechanistic studies and clinical translation of corresponding therapies. In this review, we present a comprehensive summary of the mechanisms by which TAMs dynamically polarize to influence intratumoral T cells, with a focus on their interaction with other TME cells and metabolic competition. For each mechanism, we also discuss relevant therapeutic opportunities, including non-specific and targeted approaches in combination with checkpoint inhibitors and cellular therapies. Our ultimate goal is to develop macrophage-centered therapies that can fine-tune tumor inflammation and empower immunotherapy. Frontiers Media S.A. 2023-05-12 /pmc/articles/PMC10219223/ /pubmed/37251409 http://dx.doi.org/10.3389/fimmu.2023.1160340 Text en Copyright © 2023 Han, Dong, Wu and Ma 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 Immunology
Han, Jiashu
Dong, Luochu
Wu, Mengwei
Ma, Fei
Dynamic polarization of tumor-associated macrophages and their interaction with intratumoral T cells in an inflamed tumor microenvironment: from mechanistic insights to therapeutic opportunities
title Dynamic polarization of tumor-associated macrophages and their interaction with intratumoral T cells in an inflamed tumor microenvironment: from mechanistic insights to therapeutic opportunities
title_full Dynamic polarization of tumor-associated macrophages and their interaction with intratumoral T cells in an inflamed tumor microenvironment: from mechanistic insights to therapeutic opportunities
title_fullStr Dynamic polarization of tumor-associated macrophages and their interaction with intratumoral T cells in an inflamed tumor microenvironment: from mechanistic insights to therapeutic opportunities
title_full_unstemmed Dynamic polarization of tumor-associated macrophages and their interaction with intratumoral T cells in an inflamed tumor microenvironment: from mechanistic insights to therapeutic opportunities
title_short Dynamic polarization of tumor-associated macrophages and their interaction with intratumoral T cells in an inflamed tumor microenvironment: from mechanistic insights to therapeutic opportunities
title_sort dynamic polarization of tumor-associated macrophages and their interaction with intratumoral t cells in an inflamed tumor microenvironment: from mechanistic insights to therapeutic opportunities
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10219223/
https://www.ncbi.nlm.nih.gov/pubmed/37251409
http://dx.doi.org/10.3389/fimmu.2023.1160340
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