Classical Hodgkin Lymphoma with Reduced β2M/MHC Class I Expression Is Associated with Inferior Outcome Independent of 9p24.1 Status

被引：151

作者：

Roemer, Margaretha G. M. ^{[1
,2
]}

Advani, Ranjana H. ^{[3
]}

Redd, Robert A. ^{[4
]}

Pinkus, Geraldine S. ^{[5
]}

Natkunam, Yasodha ^{[3
]}

Ligon, Azra H. ^{[5
]}

Connelly, Courtney F. ^{[1
]}

Pak, Christine J. ^{[1
]}

Carey, Christopher D. ^{[5
]}

Daadi, Sarah E. ^{[3
]}

Chapuy, Bjoern ^{[1
]}

De Jong, Daphne ^{[2
]}

Hoppe, Richard T. ^{[3
]}

Neuberg, Donna S. ^{[4
]}

Shipp, Margaret A. ^{[1
]}

Rodig, Scott J. ^{[5
]}

机构：

[1] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[2] Vrije Univ Amsterdam, Med Ctr, Dept Pathol, Amsterdam, Netherlands

[3] Stanford Univ, Med Ctr, Stanford, CA 94305 USA

[4] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA

[5] Brigham & Womens Hosp, Dept Pathol, Amory 3rd Floor,75 Francis St, Boston, MA 02115 USA

来源：

CANCER IMMUNOLOGY RESEARCH | 2016年 / 4卷 / 11期

关键词：

REED-STERNBERG CELLS; MHC CLASS-I; HLA-CLASS-I; PD-1; BLOCKADE; CANCER; RESISTANCE; NIVOLUMAB;

D O I：

10.1158/2326-6066.CIR-16-0201

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

In classical Hodgkin lymphoma (cHL), malignant Hodgkin Reed-Sternberg (HRS) cells evade antitumor immunity by multiple mechanisms, including perturbed antigen presentation and enhanced PD-1 signaling. HRS cell expression of the PD-1 ligands is attributable, in part, to copy number alterations of 9p24.1/CD274(PD-L1)/PDCD1LG2(PD-L2). Amplification of PD-L1/PD-L2 is associated with advanced clinical stage and inferior progression-free survival (PFS) following first-line (induction) therapy. The relationships between altered expression of beta(2)-microglobulin (beta M-2), MHC class I, and MHC class II by HRS cells, PD-L1/PD-L2 amplification, and clinical outcome in cHL are poorly defined. We assessed these variables in diagnostic biopsy specimens from 108 patients with cHL who received uniform treatment and had long-term follow-up and found decreased/absent expression of beta M-2/MHC class I in 79% (85/108) and decreased/absent expression of MHC class II in 67% (72/108) of cases. Patients with decreased/absent beta M-2/MHC class I had shorter PFS, independent of PD-L1/PD-L2 amplification and advanced stage. Decreased or absent MHC class II was unrelated to outcome. These results suggest that MHC class I-mediated antigen presentation by HRS cells is an important component of the biological response to standard chemo/radiotherapy. The paucity of beta M-2/MHC class I expression on HRS cells also prompts speculation regarding alternative mechanisms of action of PD-1 blockade in cHL. (C) 2016 AACR.

引用

页码：910 / 916

页数：7

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