Abstract:
:Primary central nervous system lymphoma (PCNSL) is confined to the brain, eyes, and cerebrospinal fluid without evidence of systemic spread. Rarely, PCNSL occurs in the context of immunosuppression, e.g. post-transplant lymphoproliferative disorders (PTLD) or HIV (AIDS-related PCNSL). These cases are poorly characterized, have dismal outcome and are typically Epstein-Barr virus (EBV)-tissue positive. We used targeted sequencing and digital multiplex gene expression to compare the genetic landscape and tumor microenvironment (TME) of 91 PCNSL tissues all with diffuse large B-cell lymphoma histology. 47 were EBV-tissue negative: 45 EBV(-) HIV(-) PCNSL, 2 EBV(-) HIV(+) PCNSL; and 44 were EBV-tissue positive: 23 EBV(+) HIV(+) PCNSL, 21 EBV(+) HIV(-) PCNSL. As with prior studies, EBV(-) HIV(-) PCNSL had frequent MYD88, CD79B and PIM1 mutations, and enrichment for the activated B-cell (ABC) cell-of-origin (COO) sub-type. In contrast, these mutations were absent in all EBV-tissue positive cases and ABC frequency was low. Furthermore, copy number loss in HLA-class I/II and antigen presenting/processing genes were rarely observed, indicating retained antigen presentation. To counter this, EBV(+) HIV(-) PCNSL had a tolerogenic TME with elevated macrophage and immune-checkpoint gene expression, whereas AIDS-related PCNSL had low CD4 gene counts. EBV-tissue positive PCNSL in the immunosuppressed is immunobiologically distinct from EBV(-) HIV(-) PCNSL, and despite expressing an immunogenic virus retains the ability to present EBV-antigens. Results provide a framework for targeted treatment.
journal_name
Bloodjournal_title
Bloodauthors
Gandhi MK,Hoang T,Law SC,Brosda S,O'Rourke K,Tobin JWD,Vari F,Murigneux V,Fink JL,Gunawardana J,Gould CM,Oey H,Bednarska K,Delecluse S,Trappe RU,de Long LM,Sabdia MB,Bhagat G,Hapgood G,Blyth E,Clancy LE,Wight Jdoi
10.1182/blood.2020008520subject
Has Abstractpub_date
2020-11-17 00:00:00eissn
0006-4971issn
1528-0020pii
474186pub_type
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