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

Autor: Roemer MG; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Department of Pathology, VU University Medical Center, Amsterdam, the Netherlands., Advani RH; Stanford University Medical Center, Stanford, California., Redd RA; Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts., Pinkus GS; Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts., Natkunam Y; Stanford University Medical Center, Stanford, California., Ligon AH; Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts., Connelly CF; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts., Pak CJ; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts., Carey CD; Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts., Daadi SE; Stanford University Medical Center, Stanford, California., Chapuy B; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts., de Jong D; Department of Pathology, VU University Medical Center, Amsterdam, the Netherlands., Hoppe RT; Stanford University Medical Center, Stanford, California., Neuberg DS; Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts., Shipp MA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts., Rodig SJ; Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts. srodig@partners.org.
Jazyk: angličtina
Zdroj: Cancer immunology research [Cancer Immunol Res] 2016 Nov; Vol. 4 (11), pp. 910-916. Date of Electronic Publication: 2016 Oct 13.
DOI: 10.1158/2326-6066.CIR-16-0201
Abstrakt: 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 β 2 -microglobulin (β 2 M), 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 β 2 M/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 β 2 M/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 β 2 M/MHC class I expression on HRS cells also prompts speculation regarding alternative mechanisms of action of PD-1 blockade in cHL. Cancer Immunol Res; 4(11); 910-6. ©2016 AACR.
Competing Interests: Drs. Rodig and Shipp receive research funding from Bristol-Myers Squibb
(©2016 American Association for Cancer Research.)
Databáze: MEDLINE
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