Leveraging the synergy between anti-angiogenic therapy and immune checkpoint inhibitors to treat digestive system cancers

Sep 22, 2026

Digestive system cancers often show heterogeneous, frequently disappointing responses to immunotherapy because tumor immune environments are complex and lack a single reliable predictive biomarker. Anti-angiogenic therapy and immune checkpoint inhibitors can act synergistically: vascular normalization improves blood flow and oxygenation, supporting immune-cell infiltration and reducing immunosuppressive factors. This review summarizes vasculature-immunity crosstalk in the tumor microenvironment and highlights recent advances in combining anti-angiogenic strategies with immune checkpoint blockade to enhance anti-tumor efficacy and patient outcomes.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages16

Reading Time40 min

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Introduction

Tumor immunotherapy and immune checkpoint inhibitors

Tumor angiogenesis and anti-angiogenic therapy

TYPE Review PUBLISHED 03 December 2024 DOI 10.3389/fimmu.2024.1487610 OPEN ACCESS EDITED BY Ioannis Vathiotis, National and Kapodistrian University of Athens, Greece REVIEWED BY Saptak Banerjee, Chittaranjan National Cancer Institute (CNCI), India Swapna Chaudhuri, Chittaranjan National Cancer Institute (CNCI), India *CORRESPONDENCE Dong Shao [shd645@sohu.com](shd645@sohu.com) RECEIVED 28 August 2024 ACCEPTED 20 November 2024 PUBLISHED 03 December 2024 CITATION Xu Q and Shao D (2024) Leveraging the synergy between anti-angiogenic therapy and immune checkpoint inhibitors to treat digestive system cancers. Front. Immunol. 15:1487610 . doi: 10.3389/fimmu.2024.1487610 COPYRIGHT © 2024 Xu and Shao. 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. Leveraging the synergy between anti-angiogenic therapy and immune checkpoint inhibitors to treat digestive system cancers Qinlan Xu and Dong Shao* Department of Gastroenterology, The Third Afﬁliated Hospital of Soochow University, Changzhou, Jiangsu, China The response rates to immunotherapy vary widely depending on the type of cancer and the speciﬁc treatment used and can be disappointingly low for many solid tumors. Fortunately, due to their complementary mechanisms of action, immunotherapy and anti-angiogenic therapy have synergistic effects in cancer treatment. By normalizing the tumor vasculature, anti-angiogenic therapy can improve blood ﬂow and oxygenation to facilitate better immune cell inﬁltration into the tumor and enhance the effectiveness of immunotherapy. It also reduces immunosuppressive factors and enhances immune activation, to create a more favorable environment for immune cells to attack the tumor. Their combination leverages the strengths of both therapies to enhance anti-tumor effects and improve patient outcomes. This review discusses the vasculature-immunity crosstalk in the tumor microenvironment and summarizes the latest advancesin combining anti-angiogenic therapy and immune checkpoint inhibitors to treat digestive system tumors. KEYWORDS digestive system cancer, anti-angiogenic therapy, immune checkpoint blockade, tumor microenvironment, immunotherapy, vessel normalization 1 Introduction Tumor immunotherapy harnesses the body’s immune system to ﬁght cancer and is a transformative approach to cancer treatment (1) . It is at the forefront of cancer medicine, providing new hope for patients and reshaping the therapeutic landscape. Immune checkpoint inhibitors (ICIs) form a key branch in the ﬁeld of tumor immunotherapy, and as of mid-2023, eleven ICIs have been approved by the FDA for treating 20 cancer types. To avoid being attacked by the immune system, cancer cells make use of immune checkpoint proteins (e.g., CTLA-4, PD-1, PD-L1) that maintain self-tolerance and prevent autoimmunity (2) . ICIs can block these checkpoint proteins, to thus release the brakes on the immune system and allow T cells to recognize and kill cancer cells (3) . ICIs have shown broad bioactivity and lasting effects in treating a wide range of cancers, including Frontiers in Immunology 01 [frontiersin.org](frontiersin.org) melanoma, lung cancer, kidney cancer, bladder cancer, head and neck cancers, etc., thus vastly improving the standard of care (4, 5) . However, due to the complexity of the immune environment, it is hard to predict how patients respond to ICIs before deploying the treatment, and there is no single biomarker that can offer satisfactory explanation (6, 7) . Treatment-related toxicities are also intricate, since IC

FAQs

Why do responses to immune checkpoint inhibitors vary across digestive system cancers?

Responses vary due to differences in cancer type, treatment regimen, and the complexity of the immune environment. There is also no single biomarker that satisfactorily explains patient outcomes before treatment.

How does anti-angiogenic therapy enhance immunotherapy?

Anti-angiogenic therapy can normalize tumor vasculature, improving blood flow and oxygenation. This facilitates immune-cell infiltration, reduces immunosuppressive factors, and creates a more favorable environment for immune activation against tumors.

What is the role of tumor angiogenesis in cancer progression and immune suppression?

Tumor angiogenesis supports tumor growth and survival, promotes metastasis, impairs drug delivery, worsens hypoxia and acidosis, and contributes to immune suppression. Controlling angiogenesis is therefore a key cancer-therapy strategy.

Sep 22, 2026

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