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

Cancer Immunol Res. 2016 Nov;4(11):910-916. doi: 10.1158/2326-6066.CIR-16-0201. Epub 2016 Oct 13.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antigen Presentation / immunology
  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / metabolism
  • Chromosome Aberrations*
  • Chromosomes, Human, Pair 9*
  • Female
  • Gene Expression*
  • Histocompatibility Antigens Class I / genetics*
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class I / metabolism
  • Histocompatibility Antigens Class II / genetics
  • Histocompatibility Antigens Class II / metabolism
  • Hodgkin Disease / genetics*
  • Hodgkin Disease / immunology
  • Hodgkin Disease / mortality*
  • Hodgkin Disease / therapy
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Programmed Cell Death 1 Ligand 2 Protein / genetics
  • Programmed Cell Death 1 Ligand 2 Protein / metabolism
  • Young Adult
  • beta 2-Microglobulin / genetics*
  • beta 2-Microglobulin / immunology
  • beta 2-Microglobulin / metabolism

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • PDCD1LG2 protein, human
  • Programmed Cell Death 1 Ligand 2 Protein
  • beta 2-Microglobulin