Open AccessGenetic mechanisms of HLA-I loss and immune escape in diffuse large B cell lymphoma
Author(s) -
Marco Fangazio,
Erik Ladewig,
Karen Gómez,
Laura Garcia-Ibanez,
Rahul Kumar,
Julie TeruyaFeldstein,
Davide Rossi,
Ioan Filip,
Qiang PanHammarström,
Giorgio Inghirami,
Renzo Boldorini,
German Ott,
Annette M. Staiger,
Björn Chapuy,
Gianluca Gaïdano,
Govind Bhagat,
Katia Basso,
Raúl Rabadán,
Laura Pasqualucci,
Riccardo DallaFavera
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2104504118
Subject(s) - major histocompatibility complex , biology , immune system , human leukocyte antigen , mhc class i , diffuse large b cell lymphoma , immunology , lymphoma , ciita , genetics , mhc class ii , antigen
Significance Fifty percent of diffuse large B cell lymphoma (DLBCL) evade immune-surveillance via somatic genetic lesions abrogating the expression of the class I major histocompatibility complex (MHC-I) complex on the cell surface, thus preventing the presentation of tumor neoantigens to the immune system. The results herein significantly extend these findings by showing that an additional 40% of DLBCL cases, despite expressing MHC-I, carry monoallelic HLA-I genetic alterations that limit the repertoire of neoantigens for presentation to immune cells. Both MHC-INEG and MHC-IPOS /monoallelically disrupted cases have significantly higher mutational load. Notably, homozygosis of HLA-I loci is significantly and preferentially enriched in the germline of DLBCL patients, suggesting a stepwise process by which limited neoantigen presentation is selected during DLBCL development.