Genetic mechanisms of HLA-I loss and immune escape in diffuse large B cell lymphoma.

ABSTRACT: Fifty percent of diffuse large B cell lymphoma (DLBCL) cases lack cell-surface expression of the class I major histocompatibility complex (MHC-I), thus escaping recognition by cytotoxic T cells. Here we show that, across B cell lymphomas, loss of MHC-I, but not MHC-II, is preferentially restricted to DLBCL. To identify the involved mechanisms, we performed whole exome and targeted HLA deep-sequencing in 74 DLBCL samples, and found somatic inactivation of B2M and the HLA-I loci in 80% (34 of 42) of MHC-I^NEG tumors. Furthermore, 70% (22 of 32) of MHC-I^POS DLBCLs harbored monoallelic HLA-I genetic alterations (MHC-I^POS/mono), indicating allele-specific inactivation. MHC-I^NEG and MHC-I^POS/mono cases harbored significantly hig

SUBMITTER: Fangazio M 

PROVIDER: S-EPMC8179151 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature