Gefitinib enhances the anti-tumor immune response against EGFR-mutated NSCLC by upregulating B7H5 expression and activating T cells via CD28H

doi:10.3892/ijo.2022.5436

	Gefitinib enhances the anti-tumor immune response against EGFR-mutated NSCLC by upregulating B7H5 expression and activating T cells via CD28H
	Guo, Huihui 5; Zhang, Xilin 5; Xie, Shangzhi 2; Chen, Tianwei 4; Xie, Dong 3; Cai, Ying 2; Cui, Dawei 1; Wang, Liang 6; Chen, Wei 2,8; Wang, Xiang 4,7
刊名	INTERNATIONAL JOURNAL OF ONCOLOGY
	2022-12-01
卷号	61
关键词	gefitinib CD28H NSCLC EGFR mutation
ISSN号	1019-6439
DOI	10.3892/ijo.2022.5436
通讯作者	Chen, Wei(viogro@163.com) ; Wang, Xiang(wangxiang2021@zju.edu.cn)
英文摘要	Gefitinib is a sensitive and effective drug to treat non-small-cell lung cancer (NSCLC) carrying the somatic activating mutations of the tyrosine kinase domain of epidermal growth factor receptor (EGFR). In the present study, a new mechanism of action of gefitinib in EGFR-mutated NSCLC cells was discovered using in vitro co-culture of NSCLC cells with peripheral blood mononuclear cells (PBMCs). Gefitinib significantly enhanced the cytotoxicity of PBMCs against NSCLC cells expressing mutated EGFR but not in cells expressing wild-type EGFR. Furthermore, it was observed that B7H5 expression was significantly lower in EGFR-mutant cells than in wild-type cells, while inhibition of EGFR by gefitinib or reduction in EGFR using a small interfering RNA (siRNA) both increased the expression of B7H5 in EGFR-mutated NSCLC cells. In addition, when B7H5 expression was reduced by siRNA, the toxic effect of gefitinib was reduced in the co-culture of PBMCs and EGFR-mutant NSCLC cells. In addition, the siRNA-mediated decrease in expression of the B7H5 receptor CD28H in PBMCs also reduced the toxicity of gefitinib on EGFR-mutated NSCLC. Based on these results, it may be proposed that the B7H5/CD28H axis is involved in NSCLC-mediated immunosuppression when EGFR is overactivated. Gefitinib actively inhibits mutated EGFR, which induces B7H5 expression on the cell surface of NSCLC cells, thereby activating CD28H signaling in immune cells, followed by enhanced cytotoxicity against NSCLC. The present study not only provided new insight into the immune evasion mechanism mediated by EGFR mutations but also identified new targets for immune therapy.
WOS关键词	FAMILY
WOS研究方向	Oncology
语种	英语
出版者	SPANDIDOS PUBL LTD
WOS记录号	WOS:000873733100001
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/129448]
专题	中国科学院合肥物质科学研究院
通讯作者	Chen, Wei; Wang, Xiang
作者单位	1.Zhejiang Univ, Affiliated Hosp 1, Sch Med, Dept Blood Transfus, Hangzhou 310003, Zhejiang, Peoples R China 2.Tongde Hosp Zhejiang Prov, Canc Inst Integrated Tradit Chinese & Western Med, Zhejiang Acad Tradit Chinese Med, Key Lab Canc Prevent & Therapy Combining Tradit Ch, Hangzhou 310012, Zhejiang, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Nutr & Hlth, Shanghai 200031, Peoples R China 4.Zhejiang Univ, Affiliated Hangzhou Peoples Hosp 1, Sch Med, Key Lab Integrated Oncol & Intelligent Med Zhejian, Hangzhou 310006, Zhejiang, Peoples R China 5.Huzhou Univ, Affiliated Hosp 1, Zhejiang Prov Key Lab Media Biol & Pathogen Contro, Cent Lab, Huzhou 313000, Zhejiang, Peoples R China 6.Univ Chinese Acad Sci, Canc Hosp, Zhejiang Canc Hosp, Dept Thorac Surg, Hangzhou 310022, Zhejiang, Peoples R China 7.Zhejiang Univ, Affiliated Hangzhou Peoples Hosp 1, Sch Med, Key Lab Integrated Oncol & Intelligent Med Zhejian, 261 Huansha Rd, Hangzhou 310006, Zhejiang, Peoples R China 8.Tongde Hosp Zhejiang Prov, Canc Inst Integrated Tradit Chinese & Western Med, Zhejiang Acad Tradit Chinese Med, Key Lab Canc Prevent & Therapy Combining Tradit Ch, 234 Gucui Rd, Hangzhou 310012, Zhejiang, Peoples R China
推荐引用方式 GB/T 7714	Guo, Huihui,Zhang, Xilin,Xie, Shangzhi,et al. Gefitinib enhances the anti-tumor immune response against EGFR-mutated NSCLC by upregulating B7H5 expression and activating T cells via CD28H[J]. INTERNATIONAL JOURNAL OF ONCOLOGY,2022,61.
APA	Guo, Huihui.,Zhang, Xilin.,Xie, Shangzhi.,Chen, Tianwei.,Xie, Dong.,...&Wang, Xiang.(2022).Gefitinib enhances the anti-tumor immune response against EGFR-mutated NSCLC by upregulating B7H5 expression and activating T cells via CD28H.INTERNATIONAL JOURNAL OF ONCOLOGY,61.
MLA	Guo, Huihui,et al."Gefitinib enhances the anti-tumor immune response against EGFR-mutated NSCLC by upregulating B7H5 expression and activating T cells via CD28H".INTERNATIONAL JOURNAL OF ONCOLOGY 61(2022).