干旱区生态环境知识资源中心(Arid): Stromal reaction inhibitor and immune-checkpoint inhibitor combination therapy attenuates excluded-type colorectal cancer in a mouse model

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DOI	10.1016/j.canlet.2020.10.041
	Stromal reaction inhibitor and immune-checkpoint inhibitor combination therapy attenuates excluded-type colorectal cancer in a mouse model
	Yorita, Naoki; Yuge, Ryo; Takigawa, Hidehiko; Ono, Atsushi; Kuwai, Toshio; Kuraoka, Kazuya; Kitadai, Yasuhiko; Tanaka, Shinji; Chayama, Kazuaki
通讯作者	Yuge, R (corresponding author), Hiroshima Univ, Hiroshima 7348551, Japan.
来源期刊	CANCER LETTERS
ISSN	0304-3835
EISSN	1872-7980
出版年	2021
卷号	498 页码:111-120
英文摘要	Despite recent advances in cancer immunotherapy, the efficacy of colorectal cancer (CRC) immunotherapy regimens is limited. This study evaluated the combined effect of an anti-PD-1 antibody and a platelet-derived growth factor receptor inhibitor (imatinib) on CRC progression using an orthotopic transplanted mouse model that reproduced the three histological phenotypes of CRC (inflamed-, excluded-, and desert-type). The frequency of each of these phenotypes in 196 human CRC tissue samples was also evaluated. Excluded-type CRC had the highest frequency in human tissue samples. In the mouse model, imatinib suppressed stromal reaction and increased sensitivity to anti-PD-1 treatment in excluded-type CRC. Antitumor effect was observed in mice with excluded-type tumors only after concomitant administration of anti-PD-1 antibody and imatinib. Immunohistological analysis revealed a reduction in stromal volume and an increase in the number of CD8-positive T cells in the tumor nest following combination therapy. RNA sequencing revealed significant activation of immune-related pathways and suppression of stromal-related pathways in transplanted tumors treated with combination therapy compared with tumors treated with anti-PD-1 antibody monotherapy. This combination therapy may prove effective for CRC cases that are unresponsive to anti-PD-1 antibody monotherapy.
英文关键词	Orthoptic mouse model Tumor phenotype Imatinib Anti-PD-1 antibody
类型	Article
语种	英语
开放获取类型	Green Submitted, Green Published
收录类别	SCI-E
WOS记录号	WOS:000600677200009
WOS关键词	FACTOR BETA-RECEPTOR ; MICROSATELLITE INSTABILITY ; HUMAN COLON ; OPEN-LABEL ; GROWTH ; CELLS ; METASTASIS ; CARCINOMAS ; EXPRESSION ; NIVOLUMAB
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/2XILL650/347769
作者单位	[Yorita, Naoki; Ono, Atsushi; Chayama, Kazuaki] Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Dept Gastroenterol & Metab, Hiroshima, Japan; [Yuge, Ryo; Takigawa, Hidehiko; Tanaka, Shinji] Hiroshima Univ Hosp, Dept Endoscopy, Hiroshima, Japan; [Kitadai, Yasuhiko] Prefectural Univ Hiroshima, Dept Hlth & Sci, Hiroshima, Japan; [Kuwai, Toshio] Kure Med Ctr, Dept Gastroenterol, Natl Hosp Org, Kure, Japan; [Kuwai, Toshio; Kuraoka, Kazuya] Chugoku Canc Ctr, Kure, Japan; [Kuraoka, Kazuya] Natl Hosp Org Kure Med Ctr, Dept Anat Pathol, Kure, Japan
推荐引用方式 GB/T 7714	Yorita, Naoki,Yuge, Ryo,Takigawa, Hidehiko,et al. Stromal reaction inhibitor and immune-checkpoint inhibitor combination therapy attenuates excluded-type colorectal cancer in a mouse model[J],2021,498:111-120.
APA	Yorita, Naoki.,Yuge, Ryo.,Takigawa, Hidehiko.,Ono, Atsushi.,Kuwai, Toshio.,...&Chayama, Kazuaki.(2021).Stromal reaction inhibitor and immune-checkpoint inhibitor combination therapy attenuates excluded-type colorectal cancer in a mouse model.CANCER LETTERS,498,111-120.
MLA	Yorita, Naoki,et al."Stromal reaction inhibitor and immune-checkpoint inhibitor combination therapy attenuates excluded-type colorectal cancer in a mouse model".CANCER LETTERS 498(2021):111-120.