Cargando…
The cross-talk between macrophages and tumor cells as a target for cancer treatment
Macrophages represent an important component of the innate immune system. Under physiological conditions, macrophages, which are essential phagocytes, maintain a proinflammatory response and repair damaged tissue. However, these processes are often impaired upon tumorigenesis, in which tumor-associa...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10682792/ https://www.ncbi.nlm.nih.gov/pubmed/38033495 http://dx.doi.org/10.3389/fonc.2023.1259034 |
_version_ | 1785151052116393984 |
---|---|
author | Aizaz, Muhammad Khan, Aakif Khan, Faisal Khan, Maria Musad Saleh, Ebraheem Abdu Nisar, Maryum Baran, Natalia |
author_facet | Aizaz, Muhammad Khan, Aakif Khan, Faisal Khan, Maria Musad Saleh, Ebraheem Abdu Nisar, Maryum Baran, Natalia |
author_sort | Aizaz, Muhammad |
collection | PubMed |
description | Macrophages represent an important component of the innate immune system. Under physiological conditions, macrophages, which are essential phagocytes, maintain a proinflammatory response and repair damaged tissue. However, these processes are often impaired upon tumorigenesis, in which tumor-associated macrophages (TAMs) protect and support the growth, proliferation, and invasion of tumor cells and promote suppression of antitumor immunity. TAM abundance is closely associated with poor outcome of cancer, with impediment of chemotherapy effectiveness and ultimately a dismal therapy response and inferior overall survival. Thus, cross-talk between cancer cells and TAMs is an important target for immune checkpoint therapies and metabolic interventions, spurring interest in it as a therapeutic vulnerability for both hematological cancers and solid tumors. Furthermore, targeting of this cross-talk has emerged as a promising strategy for cancer treatment with the antibody against CD47 protein, a critical macrophage checkpoint recognized as the “don’t eat me” signal, as well as other metabolism-focused strategies. Therapies targeting CD47 constitute an important milestone in the advancement of anticancer research and have had promising effects on not only phagocytosis activation but also innate and adaptive immune system activation, effectively counteracting tumor cells’ evasion of therapy as shown in the context of myeloid cancers. Targeting of CD47 signaling is only one of several possibilities to reverse the immunosuppressive and tumor-protective tumor environment with the aim of enhancing the antitumor response. Several preclinical studies identified signaling pathways that regulate the recruitment, polarization, or metabolism of TAMs. In this review, we summarize the current understanding of the role of macrophages in cancer progression and the mechanisms by which they communicate with tumor cells. Additionally, we dissect various therapeutic strategies developed to target macrophage–tumor cell cross-talk, including modulation of macrophage polarization, blockade of signaling pathways, and disruption of physical interactions between leukemia cells and macrophages. Finally, we highlight the challenges associated with tumor hypoxia and acidosis as barriers to effective cancer therapy and discuss opportunities for future research in this field. |
format | Online Article Text |
id | pubmed-10682792 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-106827922023-11-30 The cross-talk between macrophages and tumor cells as a target for cancer treatment Aizaz, Muhammad Khan, Aakif Khan, Faisal Khan, Maria Musad Saleh, Ebraheem Abdu Nisar, Maryum Baran, Natalia Front Oncol Oncology Macrophages represent an important component of the innate immune system. Under physiological conditions, macrophages, which are essential phagocytes, maintain a proinflammatory response and repair damaged tissue. However, these processes are often impaired upon tumorigenesis, in which tumor-associated macrophages (TAMs) protect and support the growth, proliferation, and invasion of tumor cells and promote suppression of antitumor immunity. TAM abundance is closely associated with poor outcome of cancer, with impediment of chemotherapy effectiveness and ultimately a dismal therapy response and inferior overall survival. Thus, cross-talk between cancer cells and TAMs is an important target for immune checkpoint therapies and metabolic interventions, spurring interest in it as a therapeutic vulnerability for both hematological cancers and solid tumors. Furthermore, targeting of this cross-talk has emerged as a promising strategy for cancer treatment with the antibody against CD47 protein, a critical macrophage checkpoint recognized as the “don’t eat me” signal, as well as other metabolism-focused strategies. Therapies targeting CD47 constitute an important milestone in the advancement of anticancer research and have had promising effects on not only phagocytosis activation but also innate and adaptive immune system activation, effectively counteracting tumor cells’ evasion of therapy as shown in the context of myeloid cancers. Targeting of CD47 signaling is only one of several possibilities to reverse the immunosuppressive and tumor-protective tumor environment with the aim of enhancing the antitumor response. Several preclinical studies identified signaling pathways that regulate the recruitment, polarization, or metabolism of TAMs. In this review, we summarize the current understanding of the role of macrophages in cancer progression and the mechanisms by which they communicate with tumor cells. Additionally, we dissect various therapeutic strategies developed to target macrophage–tumor cell cross-talk, including modulation of macrophage polarization, blockade of signaling pathways, and disruption of physical interactions between leukemia cells and macrophages. Finally, we highlight the challenges associated with tumor hypoxia and acidosis as barriers to effective cancer therapy and discuss opportunities for future research in this field. Frontiers Media S.A. 2023-11-14 /pmc/articles/PMC10682792/ /pubmed/38033495 http://dx.doi.org/10.3389/fonc.2023.1259034 Text en Copyright © 2023 Aizaz, Khan, Khan, Khan, Musad Saleh, Nisar and Baran 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 | Oncology Aizaz, Muhammad Khan, Aakif Khan, Faisal Khan, Maria Musad Saleh, Ebraheem Abdu Nisar, Maryum Baran, Natalia The cross-talk between macrophages and tumor cells as a target for cancer treatment |
title | The cross-talk between macrophages and tumor cells as a target for cancer treatment |
title_full | The cross-talk between macrophages and tumor cells as a target for cancer treatment |
title_fullStr | The cross-talk between macrophages and tumor cells as a target for cancer treatment |
title_full_unstemmed | The cross-talk between macrophages and tumor cells as a target for cancer treatment |
title_short | The cross-talk between macrophages and tumor cells as a target for cancer treatment |
title_sort | cross-talk between macrophages and tumor cells as a target for cancer treatment |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10682792/ https://www.ncbi.nlm.nih.gov/pubmed/38033495 http://dx.doi.org/10.3389/fonc.2023.1259034 |
work_keys_str_mv | AT aizazmuhammad thecrosstalkbetweenmacrophagesandtumorcellsasatargetforcancertreatment AT khanaakif thecrosstalkbetweenmacrophagesandtumorcellsasatargetforcancertreatment AT khanfaisal thecrosstalkbetweenmacrophagesandtumorcellsasatargetforcancertreatment AT khanmaria thecrosstalkbetweenmacrophagesandtumorcellsasatargetforcancertreatment AT musadsalehebraheemabdu thecrosstalkbetweenmacrophagesandtumorcellsasatargetforcancertreatment AT nisarmaryum thecrosstalkbetweenmacrophagesandtumorcellsasatargetforcancertreatment AT barannatalia thecrosstalkbetweenmacrophagesandtumorcellsasatargetforcancertreatment AT aizazmuhammad crosstalkbetweenmacrophagesandtumorcellsasatargetforcancertreatment AT khanaakif crosstalkbetweenmacrophagesandtumorcellsasatargetforcancertreatment AT khanfaisal crosstalkbetweenmacrophagesandtumorcellsasatargetforcancertreatment AT khanmaria crosstalkbetweenmacrophagesandtumorcellsasatargetforcancertreatment AT musadsalehebraheemabdu crosstalkbetweenmacrophagesandtumorcellsasatargetforcancertreatment AT nisarmaryum crosstalkbetweenmacrophagesandtumorcellsasatargetforcancertreatment AT barannatalia crosstalkbetweenmacrophagesandtumorcellsasatargetforcancertreatment |