Int J Biol Sci 2022; 18(9):3845-3858. doi:10.7150/ijbs.70958 This issue

Review

VEGF/VEGFR-Targeted Therapy and Immunotherapy in Non-small Cell Lung Cancer: Targeting the Tumor Microenvironment

Yueshui Zhao1,3,4#✉, Sipeng Guo1,3#, Jian Deng1,3#, Jing Shen1,3,4, Fukuan Du1,3,4, Xu Wu1,3,4, Yu Chen1,3,4, Mingxing Li1,3,4, Meijuan Chen1,2, Xiaobing Li1,3, Wanping Li1,3, Li Gu1,3, Yuhong Sun1,3, Qinglian Wen2,3,4, Jing Li5,6✉, Zhangang Xiao2,3,4✉

1. Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, China
2. Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China
3. Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Luzhou, Sichuan 646000, China
4. South Sichuan Institute of Translational Medicine, Luzhou, Sichuan 646000, China
5. Department of Oncology and Hematology, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China
6. Center of Excellence for Molecular Imaging (CEMI), Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand
# These authors contributed equally to this work.

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Citation:
Zhao Y, Guo S, Deng J, Shen J, Du F, Wu X, Chen Y, Li M, Chen M, Li X, Li W, Gu L, Sun Y, Wen Q, Li J, Xiao Z. VEGF/VEGFR-Targeted Therapy and Immunotherapy in Non-small Cell Lung Cancer: Targeting the Tumor Microenvironment. Int J Biol Sci 2022; 18(9):3845-3858. doi:10.7150/ijbs.70958. Available from https://www.ijbs.com/v18p3845.htm

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Abstract

Graphic abstract

Non-small cell lung cancer (NSCLC) is the leading cause of death by cancer worldwide. Despite developments in therapeutic approaches for the past few decades, the 5-year survival rate of patients with NSCLC remains low. NSCLC tumor is a complex, heterogeneous microenvironment, comprising blood vessels, cancer cells, immune cells, and stroma cells. Vascular endothelial growth factors (VEGFs) are a major mediator to induce tumor microvasculature and are associated with the progression, recurrence, and metastasis of NSCLC. Current treatment medicines targeting VEGF/VEGF receptor (VEGFR) pathway, including neutralizing antibodies to VEGF or VEGFR and receptor tyrosine kinase inhibitors, have shown good treatment efficacy in patients with NSCLC. VEGF is not only an important angiogenic factor but also an immunomodulator of tumor microenvironment (TME). VEGFs can suppress antigen presentation, stimulate activity of regulatory T (Treg) cells, and tumor-associated macrophages, which in turn promote an immune suppressive microenvironment in NSCLC. The present review focuses on the angiogenic and non-angiogenic functions of VEGF in NSCLC, especially the interaction between VEGF and the cellular components of the TME. Additionally, we discuss recent preclinical and clinical studies to explore VEGF/VEGFR-targeted compounds and immunotherapy as novel approaches targeting the TME for the treatment of NSCLC.

Keywords: NSCLC, tumor microenvironment, VEGF/VEGFR pathway, immunotherapy, clinical trials