Combined Genetic Inactivation of b2-Microglobulin and CD58 Reveals Frequent Escape from Immune Recognition in Diffuse Large B Cell Lymphoma

Challa-Malladi, Madhavi; Lieu, Yen K.; Califano, Olivia; Holmes, Antony B.; Bhagat, Govind; Vundavalli, Murty V.; Dominguez-Sola, David; Pasqualucci, Laura; Dalla-Favera, Riccardo

We report that diffuse large B cell lymphoma (DLBCL) commonly fails to express cell-surface molecules necessary for the recognition of tumor cells by immune-effector cells. In 29% of cases, mutations and dele- tions inactivate the b2-Microglobulin gene, thus preventing the cell-surface expression of the HLA class-I (HLA-I) complex that is necessary for recognition by CD8+ cytotoxic T cells. In 21% of cases, analogous lesions involve the CD58 gene, which encodes a molecule involved in T and natural killer cell-mediated responses. In addition to gene inactivation, alternative mechanisms lead to aberrant expression of HLA-I and CD58 in >60% of DLBCL. These two events are significantly associated in this disease, suggesting that they are coselected during lymphomagenesis for their combined role in escape from immune-surveillance.


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Academic Units
Biological Sciences
Institute for Cancer Genetics
Pathology and Cell Biology
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February 25, 2020