Enhancing antitumor immunity: the role of immune checkpoint inhibitors, anti-angiogenic therapy, and macrophage reprogramming

Cancer treatment has long been hindered by the complexity of the tumor microenvironment (TME) and the mechanisms that tumors employ to evade immune detection. Recently, the combination of immune checkpoint inhibitors (ICIs) and anti-angiogenic therapies has emerged as a promising approach to improve...

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Main Authors: Chong Zhang, Hua Wang, Xinying Li, Yuxin Jiang, Guoping Sun, Hanqing Yu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2025.1526407/full
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author Chong Zhang
Hua Wang
Hua Wang
Xinying Li
Yuxin Jiang
Guoping Sun
Hanqing Yu
author_facet Chong Zhang
Hua Wang
Hua Wang
Xinying Li
Yuxin Jiang
Guoping Sun
Hanqing Yu
author_sort Chong Zhang
collection DOAJ
description Cancer treatment has long been hindered by the complexity of the tumor microenvironment (TME) and the mechanisms that tumors employ to evade immune detection. Recently, the combination of immune checkpoint inhibitors (ICIs) and anti-angiogenic therapies has emerged as a promising approach to improve cancer treatment outcomes. This review delves into the role of immunostimulatory molecules and ICIs in enhancing anti-tumor immunity, while also discussing the therapeutic potential of anti-angiogenic strategies in cancer. In particular, we highlight the critical role of endoplasmic reticulum (ER) stress in angiogenesis. Moreover, we explore the potential of macrophage reprogramming to bolster anti-tumor immunity, with a focus on restoring macrophage phagocytic function, modulating hypoxic tumor environments, and targeting cytokines and chemokines that shape immune responses. By examining the underlying mechanisms of combining ICIs with anti-angiogenic therapies, we also review recent clinical trials and discuss the potential of biomarkers to guide and predict treatment efficacy.
format Article
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institution DOAJ
issn 2234-943X
language English
publishDate 2025-04-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Oncology
spelling doaj-art-9c60c0822b1d4cac8e2db1900992ff712025-08-20T03:17:54ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-04-011510.3389/fonc.2025.15264071526407Enhancing antitumor immunity: the role of immune checkpoint inhibitors, anti-angiogenic therapy, and macrophage reprogrammingChong Zhang0Hua Wang1Hua Wang2Xinying Li3Yuxin Jiang4Guoping Sun5Hanqing Yu6Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, ChinaDepartment of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, ChinaInflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei, ChinaDepartment of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, ChinaDepartment of Nephrology, The First Affiliated Hospital of Anhui Medical University, Hefei, ChinaDepartment of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, ChinaDepartment of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, ChinaCancer treatment has long been hindered by the complexity of the tumor microenvironment (TME) and the mechanisms that tumors employ to evade immune detection. Recently, the combination of immune checkpoint inhibitors (ICIs) and anti-angiogenic therapies has emerged as a promising approach to improve cancer treatment outcomes. This review delves into the role of immunostimulatory molecules and ICIs in enhancing anti-tumor immunity, while also discussing the therapeutic potential of anti-angiogenic strategies in cancer. In particular, we highlight the critical role of endoplasmic reticulum (ER) stress in angiogenesis. Moreover, we explore the potential of macrophage reprogramming to bolster anti-tumor immunity, with a focus on restoring macrophage phagocytic function, modulating hypoxic tumor environments, and targeting cytokines and chemokines that shape immune responses. By examining the underlying mechanisms of combining ICIs with anti-angiogenic therapies, we also review recent clinical trials and discuss the potential of biomarkers to guide and predict treatment efficacy.https://www.frontiersin.org/articles/10.3389/fonc.2025.1526407/fullICISangiogenesismacrophagecombination therapybiomarkers
spellingShingle Chong Zhang
Hua Wang
Hua Wang
Xinying Li
Yuxin Jiang
Guoping Sun
Hanqing Yu
Enhancing antitumor immunity: the role of immune checkpoint inhibitors, anti-angiogenic therapy, and macrophage reprogramming
Frontiers in Oncology
ICIS
angiogenesis
macrophage
combination therapy
biomarkers
title Enhancing antitumor immunity: the role of immune checkpoint inhibitors, anti-angiogenic therapy, and macrophage reprogramming
title_full Enhancing antitumor immunity: the role of immune checkpoint inhibitors, anti-angiogenic therapy, and macrophage reprogramming
title_fullStr Enhancing antitumor immunity: the role of immune checkpoint inhibitors, anti-angiogenic therapy, and macrophage reprogramming
title_full_unstemmed Enhancing antitumor immunity: the role of immune checkpoint inhibitors, anti-angiogenic therapy, and macrophage reprogramming
title_short Enhancing antitumor immunity: the role of immune checkpoint inhibitors, anti-angiogenic therapy, and macrophage reprogramming
title_sort enhancing antitumor immunity the role of immune checkpoint inhibitors anti angiogenic therapy and macrophage reprogramming
topic ICIS
angiogenesis
macrophage
combination therapy
biomarkers
url https://www.frontiersin.org/articles/10.3389/fonc.2025.1526407/full
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