HLA dependent immune escape mechanisms in B-cell lymphomas: Implications for immune checkpoint inhibitor therapy?

Marcel Nijland, Rianne N. Veenstra, Lydia Visser, Chuanhui Xu, Kushi Kushekhar, Gustaaf W. van Imhoff, Philip M. Kluin, Anke van den Berg, Arjan Diepstra*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

49 Citations (Scopus)
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Abstract

Antigen presentation by tumor cells in the context of Human Leukocyte Antigen (HLA) is generally considered to be a prerequisite for effective immune checkpoint inhibitor therapy. We evaluated cell surface HLA class I, HLA class II and cytoplasmic HLA-DM staining by immunohistochemistry (IHC) in 389 classical Hodgkin lymphomas (cHL), 22 nodular lymphocyte predominant Hodgkin lymphomas (NLPHL), 137 diffuse large B-cell lymphomas (DLBCL), 39 primary central nervous system lymphomas (PCNSL) and 19 testicular lymphomas. We describe a novel mechanism of immune escape in which loss of HLA-DM expression results in aberrant membranous invariant chain peptide (CLIP) expression in HLA class II cell surface positive lymphoma cells, preventing presentation of antigenic peptides. In HLA class II positive cases, HLA-DM expression was lost in 49% of cHL, 0% of NLPHL, 14% of DLBCL, 3% of PCNSL and 0% of testicular lymphomas. Considering HLA class I, HLA class II and HLA-DM together, 88% of cHL, 10% of NLPHL, 62% of DLBCL, 77% of PCNSL and 87% of testicular lymphoma cases had abnormal HLA expression patterns. In conclusion, an HLA expression pattern incompatible with normal antigen presentation is common in cHL, DLBCL, PCNSL and testicular lymphoma. Retention of CLIP in HLA class II caused by loss of HLA-DM is a novel immune escape mechanism, especially prevalent in cHL. Aberrant HLA expression should be taken into account when evaluating efficacy of checkpoint inhibitors in B-cell lymphomas.

Original languageEnglish
Number of pages8
JournalOncoImmunology
Volume6
Issue number4
DOIs
Publication statusPublished - 2017

Keywords

  • Diffuse large B-cell lymphoma
  • Epstein barr virus
  • human leukocyte antigen
  • Hodgkin lymphoma
  • immune checkpoint inhibitor
  • immune evasion
  • primary central nervous system lymphoma
  • major histocompatibility complex
  • therapy response
  • CLASS-II EXPRESSION
  • REED-STERNBERG CELLS
  • CYTOTOXIC T-LYMPHOCYTES
  • POOR PATIENT SURVIVAL
  • COMPLEX CLASS-I
  • HODGKINS-LYMPHOMA
  • PROGNOSTIC-SIGNIFICANCE
  • ANTIGEN PRESENTATION
  • PROTEIN EXPRESSION
  • DR EXPRESSION

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