Apatinib Combined with Local Irradiation Leads to Systemic Tumor Control via Reversal of Immunosuppressive Tumor Microenvironment in Lung Cancer.

Abstract

PURPOSE:

This study aimed to investigate the potential systemic antitumor effects of stereotactic ablative radiotherapy (SABR) and apatinib (a novel vascular endothelial growth factor receptor 2 inhibitor) via reversing the immunosuppressive tumor microenvironment for lung carcinoma.

MATERIALS AND METHODS:

Lewis lung cancer cells were injected into C57BL/6 mice in the left hindlimb (primary tumor; irradiated) and in the right flank (secondary tumor; nonirradiated). When both tumors grew to the touchable size, mice were randomly divided into eight treatment groups. These groups received normal saline or three distinct doses of apatinib (50 mg/kg, 150 mg/kg, and 200 mg/kg) daily for 7 days, in combination with a single dose of 15 Gy radiotherapy or not to the primary tumor. The further tumor growth/regression of mice were followed and observed.

RESULTS:

For the single 15 Gy modality, tumor growth delay could only be observed at the primary tumor. When combining SABR and apatinib 200 mg/kg, significant retardation of both primary and secondary tumor growth could be observed, indicated an abscopal effect was induced. Mechanism analysis suggested that programmed death-ligand 1 expression increased with SABR was counteract by additional apatinib therapy. Furthermore, when apatinib was combined with SABR, the composition of immune cells could be changed. More importantly, this two-pronged approach evoked tumor antigen-specific immune responses and the mice were resistant to another tumor rechallenge, finally, long-term survival was improved.

CONCLUSION:

Our results suggested that the tumor microenvironment could be managed with apatinib, which was effective in eliciting an abscopal effect induced by SABR.

• Authors: Li-Jun Liang, Chen-Xi Hu, Yi-Xuan Wen, Xiao-Wei Geng, Ting Chen, Guo-Qing Gu, Lei Wang, You-You Xia, Yong Liu, Jia-Yan Fei, Jie Dong, Feng-Hua Zhao, Yiliyar Ahongjiang, Kai-Yuan Hui, Xiao-Dong Jiang
• Journal: Cancer research and treatment (Cancer Res Treat) Vol. 52 Issue 2 Pg. 406-418 (Apr 2020) ISSN: 2005-9256 [Electronic] Korea (South)
• PMID: 31476848 (Publication Type: Journal Article)

Chemical References

• Protein Kinase Inhibitors
• Pyridines
• apatinib

Topics

• Animals
• Combined Modality Therapy (methods)
• Disease Models, Animal
• Female
• Humans
• Lung Neoplasms (drug therapy, radiotherapy)
• Male
• Mice
• Mice, Inbred C57BL
• Protein Kinase Inhibitors (therapeutic use)
• Pyridines (therapeutic use)
• Tumor Microenvironment