Synergism between anti-angiogenic and immune checkpoint inhibitor drugs: A hypothesis

Venniyoor, Ajit

doi:10.1016/j.mehy.2020.110399

Cited by 5 publications

(5 citation statements)

References 80 publications

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“…Hyperprogression is defined as rapid disease progression during immunotherapy, which is associated with poor survival outcome ( 75 ). In theory, rapidly proliferative cancer cells need an abundance of blood supply for nutrition, while bevacizumab could starve these cells of blood supply and nutrients and provide potential benefit ( 76 ). However, the clinical data is absent and needs further study.…”

Section: Discussionmentioning

confidence: 99%

Combination of Immune Checkpoint Inhibitors and Anti-Angiogenic Agents in Brain Metastases From Non-Small Cell Lung Cancer

Fang

Zhao

et al. 2021

Front. Oncol.

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Brain metastases remain a critical issue in the management of non-small cell lung cancer (NSCLC) because of the high frequency and poor prognosis, with survival rates often measured in just months. The local treatment approach remains the current standard of care, but management of multiple asymptomatic brain metastases always involves systemic therapy. Given that anti-angiogenic agents and immune checkpoint inhibitors (ICIs) both target the tumor microenvironment (TME), this combination therapy has become a promising strategy in clinical practice. Increasing number of preclinical and clinical studies have shown remarkable anti-tumor activity of the combination therapy, but the efficacy in brain metastases is unclear due to the strict selection criteria adopted in most clinical trials. This review briefly summarizes the potential synergistic anti-tumor effect and clinical development of the combination of anti-angiogenic agents and ICIs in NSCLC brain metastases, and discusses the existing challenges and problems.

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Section: Discussionmentioning

confidence: 99%

Combination of Immune Checkpoint Inhibitors and Anti-Angiogenic Agents in Brain Metastases From Non-Small Cell Lung Cancer

Fang

Zhao

et al. 2021

Front. Oncol.

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“…The anti-angiogenic drug bevacizumab is known to reduce tumor vascularization, improve perfusion, and reverse VEGF-mediated immunosuppression, inducing the immunosuppressive TME to an immunostimulatory switch. An alternative proposed mechanism involved bevacizumab-induced hypoxia, which increases TMB by stress-induced mutagenesis, and thus creates a hypermutated tumor profile, rendering it more responsive to immunotherapy with atezolizumab [ 124 ].…”

Section: Tmb As Biomarker Of Therapy Outcomementioning

confidence: 99%

Tumor Mutational Burden for Predicting Prognosis and Therapy Outcome of Hepatocellular Carcinoma

Gabbia

Martin

2023

IJMS

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Hepatocellular carcinoma (HCC), the primary hepatic malignancy, represents the second-highest cause of cancer-related death worldwide. Many efforts have been devoted to finding novel biomarkers for predicting both patients’ survival and the outcome of pharmacological treatments, with a particular focus on immunotherapy. In this regard, recent studies have focused on unravelling the role of tumor mutational burden (TMB), i.e., the total number of mutations per coding area of a tumor genome, to ascertain whether it can be considered a reliable biomarker to be used either for the stratification of HCC patients in subgroups with different responsiveness to immunotherapy, or for the prediction of disease progression, particularly in relation to the different HCC etiologies. In this review, we summarize the recent advances on the study of TMB and TMB-related biomarkers in the HCC landscape, focusing on their feasibility as guides for therapy decisions and/or predictors of clinical outcome.

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“…101 It is worth noting that there is a hypothesis suggesting that anti-angiogenic drugs can induce hypoxia, and augment the effectiveness of ICIs by increasing tumor immunogenicity. 102 Tumor Mutational Burden (TMB, mutations per megabase) indicates the level of tumor mutations. It is generally believed that tumors with high TMB possess more surface neoantigens, thereby triggering a heightened immune response.…”

Section: Mechanism Of Synergistic Effect Between Anti-angiogenic Agen...mentioning

confidence: 99%

“…Moreover, hypoxic conditions promoted the naïve CD4 + T cells to differentiate into regulatory T cells (Tregs), contributing to tumor immune evasion 101 . It is worth noting that there is a hypothesis suggesting that anti‐angiogenic drugs can induce hypoxia, and augment the effectiveness of ICIs by increasing tumor immunogenicity 102 . Tumor Mutational Burden (TMB, mutations per megabase) indicates the level of tumor mutations.…”

Section: Mechanism Of Synergistic Effect Between Anti‐angiogenic Agen...mentioning

confidence: 99%

Anti‐angiogenic therapy enhances cancer immunotherapy: Mechanism and clinical application

Li,

Fang

2024

Interdisciplinary Medicine

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Immunotherapy, specifically immune checkpoint inhibitors, is revolutionizing cancer treatment, achieving durable control of previously incurable or advanced tumors. However, only a certain group of patients exhibit effective responses to immunotherapy. Anti‐angiogenic therapy aims to block blood vessel growth in tumors by depriving them of essential nutrients and effectively impeding their growth. Emerging evidence shows that tumor vessels exhibit structural and functional abnormalities, resulting in an immunosuppressive microenvironment and poor response to immunotherapy. Both preclinical and clinical studies have used anti‐angiogenic agents to enhance the effectiveness of immunotherapy against cancer. In this review, we concentrate on the synergistic effect of anti‐angiogenic and immune therapies in cancer management, dissect the direct effects and underlying mechanisms of tumor vessels on recruiting and activating immune cells, and discuss the potential of anti‐angiogenic agents to improve the effectiveness of immunotherapy. Lastly, we outline challenges and opportunities for the anti‐angiogenic strategy to enhance immunotherapy. Considering the increasing approval of the combination of anti‐angiogenic and immune therapies in treating cancers, this comprehensive review would be timely and important.

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Synergism between anti-angiogenic and immune checkpoint inhibitor drugs: A hypothesis

Cited by 5 publications

References 80 publications

Combination of Immune Checkpoint Inhibitors and Anti-Angiogenic Agents in Brain Metastases From Non-Small Cell Lung Cancer

Combination of Immune Checkpoint Inhibitors and Anti-Angiogenic Agents in Brain Metastases From Non-Small Cell Lung Cancer

Tumor Mutational Burden for Predicting Prognosis and Therapy Outcome of Hepatocellular Carcinoma

Anti‐angiogenic therapy enhances cancer immunotherapy: Mechanism and clinical application

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