title: Classical Hodgkin Lymphoma with Reduced β2M/MHC Class I Expression Is Associated with Inferior Outcome Independent of 9p24.1 Status.
abstract: 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 β2-microglobulin (β2M), 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 β2M/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 β2M/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 β2M/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.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.|Department of Pathology, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Margaretha G M
authors.initials: MG
authors.lastname: Roemer
authors.affiliation: Stanford University Medical Center, Stanford, California.
authors.forename: Ranjana H
authors.initials: RH
authors.lastname: Advani
authors.affiliation: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Redd
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Geraldine S
authors.initials: GS
authors.lastname: Pinkus
authors.affiliation: Stanford University Medical Center, Stanford, California.
authors.forename: Yasodha
authors.initials: Y
authors.lastname: Natkunam
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Azra H
authors.initials: AH
authors.lastname: Ligon
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Courtney F
authors.initials: CF
authors.lastname: Connelly
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Christine J
authors.initials: CJ
authors.lastname: Pak
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Carey
authors.affiliation: Stanford University Medical Center, Stanford, California.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Daadi
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Bjoern
authors.initials: B
authors.lastname: Chapuy
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Daphne
authors.initials: D
authors.lastname: de Jong
authors.affiliation: Stanford University Medical Center, Stanford, California.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Hoppe
authors.affiliation: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Donna S
authors.initials: DS
authors.lastname: Neuberg
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Shipp
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts. srodig@partners.org.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Rodig
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017951:Antigen Presentation / Q000276:immunology; D060890:B7-H1 Antigen / Q000235:genetics / Q000378:metabolism; D002869:Chromosome Aberrations; D002899:Chromosomes, Human, Pair 9; D005260:Female; D015870:Gene Expression; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism; D006689:Hodgkin Disease / Q000235:genetics* / Q000276:immunology / Q000401:mortality* / Q000628:therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D061027:Programmed Cell Death 1 Ligand 2 Protein / Q000235:genetics / Q000378:metabolism; D055815:Young Adult; D001613:beta 2-Microglobulin / Q000235:genetics* / Q000276:immunology / Q000378:metabolism
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; C556977:PDCD1LG2 protein, human; D061027:Programmed Cell Death 1 Ligand 2 Protein; D001613:beta 2-Microglobulin