High efficacy of PD-1 inhibitor after initial failure of PD-L1 inhibitor in Relapsed/Refractory classical Hodgkin Lymphoma.
High efficacy of PD-1 inhibitor after initial failure of PD-L1 inhibitor in Relapsed/Refractory classical Hodgkin Lymphoma.
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在 PD-L1 抑制剂治疗复发/难治性经典霍奇金淋巴瘤初期失败后，PD-1 抑制剂具有较高疗效。
DOI：
10.1186/s12885-021-09028-4
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发表时间：
2022-01-03
期刊：
影响因子：
3.8
通讯作者：
Wu M
中科院分区：
文献类型：
--
作者：
Chen X;Kong H;Luo L;Han S;Lei T;Yu H;Guo N;Li C;Peng S;Dong X;Yang H;Wu M
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. 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. 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. 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. The online version contains supplementary material available at 10.1186/s12885-021-09028-4.
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影响因子：
3.3
作者：
Panjwani, Poonam K.;Charu, Vivek;Zhao, Shuchun
通讯作者：
Zhao, Shuchun
影响因子：
20.3
作者：
Green, Michael R.;Monti, Stefano;Shipp, Margaret A.
通讯作者：
Shipp, Margaret A.
影响因子：
3.5
作者：
Klein, Jonathan L.;Nguyen, TuDung T.;Kreisel, Friederike
通讯作者：
Kreisel, Friederike
影响因子：
5.7
作者：
Oike N;Kawashima H;Ogose A;Hotta T;Hatano H;Ariizumi T;Sasaki T;Yamagishi T;Umezu H;Endo N
通讯作者：
Endo N
影响因子：
10.1
作者：
Roemer MG;Advani RH;Redd RA;Pinkus GS;Natkunam Y;Ligon AH;Connelly CF;Pak CJ;Carey CD;Daadi SE;Chapuy B;de Jong D;Hoppe RT;Neuberg DS;Shipp MA;Rodig SJ
通讯作者：
Rodig SJ