High efficacy of PD-1 inhibitor after initial failure of PD-L1 inhibitor in Relapsed/Refractory classical Hodgkin Lymphoma

doi:10.1186/s12885-021-09028-4

	High efficacy of PD-1 inhibitor after initial failure of PD-L1 inhibitor in Relapsed/Refractory classical Hodgkin Lymphoma
	Chen, Xi 2,3; Kong, Haiying 4; Luo, Linxiang 5; Han, Shuiyun 2,3; Lei, Tao 2,3; Yu, Haifeng 2,3; Guo, Na 3,6; Li, Cong 2,3; Peng, Shuailing 2,3; Dong, Xiaowu 1
刊名	BMC CANCER
	2022-01-03
卷号	22
关键词	Hodgkin lymphoma PD-1 inhibitor PD-L1 inhibitor PD-L2 Molecular phenotype Tumor microenvironment
DOI	10.1186/s12885-021-09028-4
通讯作者	Yang, Haiyan(haiyanyang1125@163.com) ; Wu, Meijuan(wumj@zjcc.org.cn)
英文摘要	Purpose: We sought to understand the clinical course and molecular phenotype of patients who showed disease progression after programmed cell death ligand 1 (PD-L1) inhibitor treatment but subsequently responded to PD-1 inhibitor treatment. We also explored the response to PD-1-axis targeted therapy of classical Hodgkin lymphoma (cHL) according to genetically driven PD-L1 and programmed cell death ligand 2 (PD-L2) expression. Methods: Five patients in a phase II clinical trial of CS1001 (PD-L1 inhibitor) for relapsed or refractory (R/R) cHL were retrospectively reviewed. Formalin-fixed, paraffin-embedded whole tissues from the five patients were evaluated for 9p24.1 genetic alterations based on FISH and the expression of PD-L1, PD-L2, PD-1, major histocompatibility complex (MHC) class I-II, and the tumor microenvironment factorsCD163 and FOXP3 in the microenvironmental niche, as revealed by multiplex immunofluorescence. Results: All five patients showed primary refractory disease during first-line treatment. Four patients received PD-1 inhibitor after dropping out of the clinical trial, and all demonstrated at least a partial response. The progression-free survival ranged from 7 to 28 months (median = 18 months), and 9p24.1 amplification was observed in all five patients at the PD-L1/PD-L2 locus. PD-L1 and PD-L2 were colocalized on Hodgkin Reed-Sternberg (HRS) cells in four of the five (80%) patients. There was differential expression of PD-L1 and PD-L2 in cells in the tumor microenvironment in cHL, especially in HRS cells, background cells and tumor-associated macrophages. Conclusions: PD-L1 monotherapy may not be sufficient to block the PD-1 pathway; PD-L2 was expressed in HRS and background cells in cHL. The immunologic function of the PD-L2 pathway in anti-tumor activity may be underestimated in R/R cHL. Further study is needed to elucidate the anti-tumor mechanism of PD-1 inhibitor and PD-L1 inhibitor treatment.
资助项目	Science and Technology Program of Zhejiang Provincial Traditional Chinese Medicine[2021ZB038]
WOS关键词	TUMOR-ASSOCIATED MACROPHAGES ; ANALYSIS REVEALS ; FOLLOW-UP ; EXPRESSION ; CELLS ; NIVOLUMAB ; BLOCKADE ; CD163 ; CD68
WOS研究方向	Oncology
语种	英语
出版者	BMC
WOS记录号	WOS:000738001600023
资助机构	Science and Technology Program of Zhejiang Provincial Traditional Chinese Medicine
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/127247]
专题	中国科学院合肥物质科学研究院
通讯作者	Yang, Haiyan; Wu, Meijuan
作者单位	1.Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou Inst Innovat Med, Hangzhou, Peoples R China 2.Univ Chinese Acad Sci, Dept Lymphoma, Canc Hosp, Zhejiang Canc Hosp, Hangzhou, Peoples R China 3.Chinese Acad Sci, Inst Canc & Basic Med IBMC, Hangzhou, Peoples R China 4.Hangzhou Hanggang Hosp, Dept Pharm, Zhejiang Med & Hlth Grp, Hangzhou Hosp, Hangzhou, Peoples R China 5.Zhejiang Quhua Hosp, Dept Hematol, Quhua, Peoples R China 6.Univ Chinese Acad Sci, Zhejiang Canc Hosp, Canc Hosp, Dept Pathol, 1 Banshan East Rd, Hangzhou, Peoples R China
推荐引用方式 GB/T 7714	Chen, Xi,Kong, Haiying,Luo, Linxiang,et al. High efficacy of PD-1 inhibitor after initial failure of PD-L1 inhibitor in Relapsed/Refractory classical Hodgkin Lymphoma[J]. BMC CANCER,2022,22.
APA	Chen, Xi.,Kong, Haiying.,Luo, Linxiang.,Han, Shuiyun.,Lei, Tao.,...&Wu, Meijuan.(2022).High efficacy of PD-1 inhibitor after initial failure of PD-L1 inhibitor in Relapsed/Refractory classical Hodgkin Lymphoma.BMC CANCER,22.
MLA	Chen, Xi,et al."High efficacy of PD-1 inhibitor after initial failure of PD-L1 inhibitor in Relapsed/Refractory classical Hodgkin Lymphoma".BMC CANCER 22(2022).