Therapeutic targeting of VEGF and/or TGF-β to enhance anti-PD-(L)1 therapy: The evidence from clinical trials

Normalizing the tumor microenvironment (TME) is a potential strategy to improve the effectiveness of immunotherapy. Vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-β pathways play an important role in the development and function of the TME, contributing to the immunos...

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Published inFrontiers in oncology Vol. 12; p. 905520
Main Authors Li, Linwei, Wen, Qinglian, Ding, Ruilin
Format Journal Article
LanguageEnglish
Published Frontiers Media S.A 26.07.2022
Subjects
immunotherapy
Oncology
PD-1
review
TGF-β
tumor microenvironment
VEGF
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Summary:Normalizing the tumor microenvironment (TME) is a potential strategy to improve the effectiveness of immunotherapy. Vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-β pathways play an important role in the development and function of the TME, contributing to the immunosuppressive status of TME. To inhibit VEGF and/or TGF-β pathways can restore TME from immunosuppressive to immune-supportive status and enhance sensitivity to immunotherapy such as programmed death protein-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) inhibitors. In this review, we described the existing preclinical and clinical evidence supporting the use of anti-VEGF and/or anti-TGF-β therapies to enhance cancer immunotherapy. Encouragingly, adopting anti-VEGF and/or anti-TGF-β therapies as a combination treatment with anti-PD-(L)1 therapy have been demonstrated as effective and tolerable in several solid tumors in clinical trials. Although several questions need to be solved, the clinical value of this combination strategy is worthy to be studied further.
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Edited by: Camillo Porta, University of Bari Aldo Moro, Italy
This article was submitted to Cancer Immunity and Immunotherapy, a section of the journal Frontiers in Oncology
These authors have contributed equally to this work and share last authorship
Reviewed by: Mototsugu Oya, Keio University, Japan; Mónica Bequet-Romero, Center for Genetic Engineering and Biotechnology (CIGB), Cuba
ISSN:2234-943X
2234-943X
DOI:10.3389/fonc.2022.905520