干旱区生态环境知识资源中心(Arid): Anti-VEGF antibody triggers the effect of anti-PD-L1 antibody in PD-L1(low) and immune desert-like mouse tumors

Arid

DOI	10.3892/or.2021.8247
	Anti-VEGF antibody triggers the effect of anti-PD-L1 antibody in PD-L1(low) and immune desert-like mouse tumors
	Ishikura, Nobuyuki; Sugimoto, Masamichi; Yorozu, Keigo; Kurasawa, Mitsue; Kondoh, Osamu
通讯作者	Ishikura, N (corresponding author), Chugai Pharmaceut Co Ltd, Prod Res Dept, 200 Kajiwara, Kamakura, Kanagawa 2478530, Japan.
来源期刊	ONCOLOGY REPORTS
ISSN	1021-335X
EISSN	1791-2431
出版年	2022
卷号	47 期号:2
英文摘要	The efficacy of programmed cell death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) blockade therapy has been demonstrated but is limited in patients with PD-L1(low) or immune desert tumors. This limitation can be overcome by combination therapies that include anti-vascular endothelial growth factor (VEGF) therapy. Such combinations have been investigated in clinical trials for a number of cancer types; however, evidence on the mechanisms underlying their effects in these types of patients is still not sufficient. Therefore, the present study investigated the efficacy and effects on CD8(+) T cell and C-X-C motif chemokine receptor 3 (CXCR3) ligand expression in tumors by combining anti-PD-L1 and anti-VEGF antibodies using an OV2944-HM-1 mouse model with PD-L1(low) and immune desert-like phenotypes. Although the model exhibited anti-PD-L1 insensitivity, anti-PD-L1 antibody treatment combined with anti-VEGF antibody inhibited tumor growth compared with anti-VEGF monotherapy, which itself inhibited tumor growth compared with the control treatment on Day 25. In combination-treated mice, a higher percentage of CD8(+) T cells and higher levels of CXCR3 ligands were observed in tumor tissues compared with those in the anti-VEGF antibody treatment group, which was not significantly different from control treatment on Day 8. The increase in the intratumoral percentage of CD8(+) T cells following the combination treatment was reversed by CXCR3 blocking to the same level as the control. In an anti-PD-L1 insensitive model with PD-L1(low) and immune desert-like phenotypes, although anti-PD-L1 antibody alone was not effective, anti-PD-L1 antibody in combination with anti-VEGF antibody exhibited antitumor combination efficacy with an increase of CD8(+) T cell infiltration, which was suggested to be dependent on the increase of intratumoral CXCR3 ligands. This mechanism could explain the efficacy of anti-PD-L1 antibody and anti-VEGF antibody combination therapy in the clinical setting.
英文关键词	anti-programmed death-ligand 1 anti-vascular endothelial growth factor atezolizumab bevacizumab C-X-C motif chemokine receptor 3 ligands immune desert
类型	Article
语种	英语
开放获取类型	hybrid
收录类别	SCI-E
WOS记录号	WOS:000736608200001
WOS关键词	ENDOTHELIAL GROWTH-FACTOR ; CANCER-IMMUNITY ; IFN-GAMMA ; CELLS ; ATEZOLIZUMAB ; ACTIVATION ; EXPRESSION ; MATURATION ; INFILTRATE ; BLOCKADE
WOS类目	Oncology
WOS研究方向	Oncology
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/374499
作者单位	[Ishikura, Nobuyuki; Sugimoto, Masamichi; Yorozu, Keigo; Kurasawa, Mitsue; Kondoh, Osamu] Chugai Pharmaceut Co Ltd, Prod Res Dept, 200 Kajiwara, Kamakura, Kanagawa 2478530, Japan
推荐引用方式 GB/T 7714	Ishikura, Nobuyuki,Sugimoto, Masamichi,Yorozu, Keigo,et al. Anti-VEGF antibody triggers the effect of anti-PD-L1 antibody in PD-L1(low) and immune desert-like mouse tumors[J],2022,47(2).
APA	Ishikura, Nobuyuki,Sugimoto, Masamichi,Yorozu, Keigo,Kurasawa, Mitsue,&Kondoh, Osamu.(2022).Anti-VEGF antibody triggers the effect of anti-PD-L1 antibody in PD-L1(low) and immune desert-like mouse tumors.ONCOLOGY REPORTS,47(2).
MLA	Ishikura, Nobuyuki,et al."Anti-VEGF antibody triggers the effect of anti-PD-L1 antibody in PD-L1(low) and immune desert-like mouse tumors".ONCOLOGY REPORTS 47.2(2022).