Augmenting Anticancer Immunity Through Combined Targeting of Angiogenic and PD-1/PD-L1 Pathways: Challenges and Opportunities

Hack, Stephen P.; Zhu, Andrew X.; Wang, Yulei

doi:10.3389/fimmu.2020.598877

Cited by 182 publications

(156 citation statements)

References 222 publications

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“…However, two years after its approval by the US Food and Drug Administration for metastatic BC, Bevacizumab was retracted due to an insufficient benefit/risk balance. It has been shown that Bevacizumab leads to a reduction of Treg in a CRC mouse model and in patients suffering from CRC [ 24 , 76 , 77 , 78 ] and increases the number of DCs in the peripheral blood [ 24 , 77 , 79 ]. Accordingly, Bevacizumab also reestablishes the ability of monocyte to differentiate into DC and restores the expression of CD86 and HLA-DR on DCs [ 65 ].…”

Section: A Whole Range Of Anti-vegf/vegfr Therapiesmentioning

confidence: 99%

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Vascular Endothelial Growth Factor, a Key Modulator of the Anti-Tumor Immune Response

Geindreau

Ghiringhelli

Bruchard

2021

IJMS

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During tumor growth, angiogenesis is required to ensure oxygen and nutrient transport to the tumor. Vascular endothelial growth factor (VEGF) is the major inducer of angiogenesis and appears to be a key modulator of the anti-tumor immune response. Indeed, VEGF modulates innate and adaptive immune responses through direct interactions and indirectly by modulating protein expressions on endothelial cells or vascular permeability. The inhibition of the VEGF signaling pathway is clinically approved for the treatment of several cancers. Therapies targeting VEGF can modulate the tumor vasculature and the immune response. In this review, we discuss the roles of VEGF in the anti-tumor immune response. In addition, we summarize therapeutic strategies based on its inhibition, and their clinical approval.

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Section: A Whole Range Of Anti-vegf/vegfr Therapiesmentioning

confidence: 99%

“…Ramucirumab increases CD8 + T cell infiltration in the TME [ 83 ]. Ramucirumab [ 83 ] and Bevacizumab [ 24 , 76 , 77 , 78 ] reduce the frequency of Treg in the TME.…”

Section: A Whole Range Of Anti-vegf/vegfr Therapiesmentioning

confidence: 99%

Vascular Endothelial Growth Factor, a Key Modulator of the Anti-Tumor Immune Response

Geindreau

Ghiringhelli

Bruchard

2021

IJMS

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“…By now, a number of randomized trials have shown remarkable results which have led to approvals by the FDA and/or EMA in renal cell carcinoma (axitinib plus pembrolizumab, and axitinib plus avelumab), endometrial carcinoma (pembrolizumab plus lenvatinib), non-squamous NSCLC (bevacizumab and atezolizumab), and hepatocellular carcinoma (bevacizumab plus atezolizumab). This broad clinical activity suggest that a combination strategy may also be of benefit in colorectal cancer [ 84 ].…”

Section: Anti-angiogenesis and Immunotherapymentioning

confidence: 99%

Angiogenesis Inhibitors for Colorectal Cancer. A Review of the Clinical Data

Hansen

Qvortrup

Pfeiffer

2021

Cancers

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Since the late 1990s, therapy for metastatic colorectal cancer (mCRC) has changed considerably, and the combination of doublet or triplet chemotherapy and a targeted agent are now routinely used. The targeting of angiogenesis, the development of new blood vessels, represents a key element in the overall treatment strategy. Since the approval in 2004 of the first anti-angiogenetic drug, multiple agents have been approved and others are currently under investigation. We present an overview of the recent literature on approved systemic treatment of mCRC, with a focus on anti-angiogenic drugs, and current treatment approaches, and elaborate on the future role of angiogenesis in colorectal cancer as seen from a clinical perspective. The treatment of mCRC, in general, has changed from “one strategy fits all” to a more personalized approach. This is, however, not entirely the case for anti-angiogenetic treatments, partly due to a lack of validated biomarkers. The anti-angiogenetic standard treatment at the present primarily includes monoclonal antibodies. The therapeutic field of angiogenesis, however, has received increased interest after the introduction of newer combinations. These approaches will likely change the current treatment strategy, once again, to the overall benefit of patients.

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“…Increasing evidence suggests that antiangiogenic agents stimulate the immune system, and that immunotherapy might also exhibit antiangiogenic effects. It has been shown that VEGF weakens the antitumor immune response through two main modes of action: first, VEGF was shown to block the infiltration of T cells into the tumor by inhibiting the adhesion of lymphocytes to activated endothelial cells; and second, VEGF was shown to promote the function of immunomodulatory cells through a variety of mechanisms ( 72 ). Considering the immunosuppressive and angiogenic effects of VEGF in tumors, it is not surprising that antiangiogenic agents stimulate the immune response and enhance the effectiveness of immunotherapy.…”

Section: Therapeutic Strategies For Different Tumor Types In His Micementioning

confidence: 99%

Strategies for the Construction of Mouse Models With Humanized Immune System and Evaluation of Tumor Immune Checkpoint Inhibitor Therapy

et al. 2021

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Immunotherapy has been used as a first-line treatment for a variety of advanced tumors, allowing remarkable progress to be made in cancer treatment. Nonetheless, only a small number of patients can benefit from immune checkpoint inhibitor monotherapy. To improve the effect of immunotherapy, the underlying mechanism of combination therapy was investigated in the context of an intact human tumor immune microenvironment using mice with a human immune system (HIS) bearing human tumors. Herein, we summarize and discuss strategies for the development and use of HIS mice models in tumor immunotherapies. Most importantly, this review proposes a method of t11umor identification and classification in HIS mice based on the tumor-infiltrating lymphocytes and PD-L1 expression, and according to this classification, we propose different combination treatment strategies that can be utilized to enhance the effect of immunotherapy. Thus, we provide effective experimental schemes for tumor immunotherapy in HIS mice models.

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Augmenting Anticancer Immunity Through Combined Targeting of Angiogenic and PD-1/PD-L1 Pathways: Challenges and Opportunities

Abstract: studies. We also discuss data from recently reported randomized clinical trials. Finally, we discuss how these concepts and approaches can be further incorporated into clinical practice to improve immunotherapy outcomes for patients with cancer.

Cited by 182 publications

References 222 publications

Vascular Endothelial Growth Factor, a Key Modulator of the Anti-Tumor Immune Response

Vascular Endothelial Growth Factor, a Key Modulator of the Anti-Tumor Immune Response

Angiogenesis Inhibitors for Colorectal Cancer. A Review of the Clinical Data

Strategies for the Construction of Mouse Models With Humanized Immune System and Evaluation of Tumor Immune Checkpoint Inhibitor Therapy

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