Synergistic effect of immune checkpoint blockade and anti-angiogenesis in cancer treatment
Open accessAbstract
Immune checkpoint inhibitor (ICI) activates host's anti-tumor immune response by blocking negative regulatory immune signals. A series of clinical trials showed that ICI could effectively induce tumor regression in a subset of advanced cancer patients. In clinical practice, a main concerning for choosing ICI is the low response rate. Even though multiple predictive biomarkers such as PD-L1 expression, mismatch-repair deficiency, and status of tumor infiltrating lymphocytes have been adopted for patient selection, frequent resistance to ICI monotherapy has not been completely resolved. However, some recent studies indicated that ICI resistance could be alleviated by combination therapy with anti-angiogenesis treatment. Actually, anti-angiogenesis therapy not only prunes blood vessel which is essential to cancer growth and metastasis, but also reprograms the tumor immune microenvironment. Preclinical studies demonstrated that the efficacy of combination therapy of ICI and anti-angiogenesis was superior to monotherapy. In mice model, combination therapy could effectively increase the ratio of anti-tumor/pro-tumor immune cell and decrease the expression of multiple immune checkpoints more than PD-1. Based on exciting results from preclinical studies, many clinical trials were deployed to investigate the synergistic effect of the combination therapy and acquired promising outcome. This review summarized the latest understanding of ICI combined anti-angiogenesis therapy and highlighted the advances of relevant clinical trials.
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Other immune checkpoints, abnormal angiogenesis, immunosuppressive immune cells or cytokines, cancer-associated adipocytes, and hyperactive cancer-associated fibroblasts also modulate the cancer-immune set point and promote immune tolerance.
“Apart from PD-1 signaling, other immune checkpoints, abnormal angiogenesis, immunosuppressive immune cells or cytokines, cancer-associated adipocytes, and hyperactive cancer-associated fibroblasts also modulate cancer-immune set point and promote immune tolerance [15–20].”
From Combination strategies with PD-1/PD-L1 blockade: current advances and future directions (2022) · cites this paper as [16]
Disorganized angiogenesis promotes the formation of the immunosuppressive TME.
“The disorganized angiogenesis promotes the formation of the immunosuppressive TME [16].”
From Combination strategies with PD-1/PD-L1 blockade: current advances and future directions (2022) · cites this paper as [16]
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References 105 · Cited by 608
- Authors
- Yi, M., Jiao, D., Qin, S., Chu, Q., Wu, K., & Li, A.
- Affiliations
- Tongji Hospital (CN)
- First Affiliated Hospital of Zhengzhou University (CN)
- Corresponding author
- Wu, Kongming
- Li, Anping
- Venue
- Molecular Cancer
- Published
- 2019-03-30
- Volume
- 18
- Issue
- 1
- Pages
- 60-60
- ISSN
- 1476-4598 (ISSN-L)
- PMC
- PMC6441150
- OpenAlex
- W2941109595
- Cited by
- 608
- References
- 105
- Citations by year
- 2026: 52 · 2025: 71 · 2024: 117 · 2023: 106 · 2022: 97 · 2021: 95 · 2020: 60 · 2019: 9
- FWCI
- 6.27
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecular Cancer (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (81874120, 81572608, 81672984)
- Wuhan Municipal Science and Technology Bureau (2017060201010170)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- immune checkpoint inhibitors, anti-angiogenic therapy, combination therapy, immune checkpoint inhibitor resistance, tumor immune microenvironment, PD-1, PD-L1, tumor-infiltrating lymphocytes, predictive biomarkers, tumor vasculature, cancer immunotherapy
- MeSH terms
- Antineoplastic Agents, Immunological, Animals, Drug Synergism, Humans, Immunotherapy, Neoplasms, Angiogenesis Inhibitors, B7-H1 Antigen, Programmed Cell Death 1 Receptor
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