Purpose Hodgkin Reed-Sternberg (HRS) cells evade antitumor immunity by multiple means, including gains of 9p24.1/ CD274(PD-L1)/ PDCD1LG2(PD-L2) and perturbed antigen presentation. Programmed death 1 (PD-1) receptor blockade is active in classic Hodgkin lymphoma (cHL) despite reported deficiencies of major histocompatibility complex (MHC) class I expression on HRS cells. Herein, we assess bases of sensitivity to PD-1 blockade in patients with relapsed/refractory cHL who were treated with nivolumab (anti-PD-1) in the CheckMate 205 trial. Methods HRS cells from archival tumor biopsies were evaluated for 9p24.1 alterations by fluorescence in situ hybridization and for expression of PD ligand 1 (PD-L1) and the antigen presentation pathway components-β2-microglobulin, MHC class I, and MHC class II-by immunohistochemistry. These parameters were correlated with clinical responses and progression-free survival (PFS) after PD-1 blockade. Results Patients with higher-level 9p24.1 copy gain and increased PD-L1 expression on HRS cells had superior PFS. HRS cell expression of β2-microglobulin/MHC class I was not predictive for complete remission or PFS after nivolumab therapy. In contrast, HRS cell expression of MHC class II was predictive for complete remission. In patients with a > 12-month interval between myeloablative autologous stem-cell transplantation and nivolumab therapy, HRS cell expression of MHC class II was associated with prolonged PFS. Conclusion Genetically driven PD-L1 expression and MHC class II positivity on HRS cells are potential predictors of favorable outcome after PD-1 blockade. In cHL, clinical responses to nivolumab were not dependent on HRS cell expression of MHC class I.

• MeSH
• antigeny CD274 antagonisté a inhibitory   biosyntéza   genetika   imunologie   MeSH
• antigeny CD279 antagonisté a inhibitory   biosyntéza   genetika   imunologie   MeSH
• beta-2-mikroglobulin biosyntéza   genetika   imunologie   MeSH
• buňky Reedové-Sternberga účinky léků   imunologie   patologie   MeSH
• doba přežití bez progrese choroby MeSH
• Hodgkinova nemoc farmakoterapie   genetika   imunologie   patologie   MeSH
• kohortové studie MeSH
• lidé MeSH
• lidské chromozomy, pár 9 MeSH
• MHC antigeny II. třídy biosyntéza   genetika   imunologie   MeSH
• nivolumab terapeutické užití   MeSH
• prediktivní hodnota testů MeSH
• prezentace antigenu MeSH
• protinádorové látky imunologicky aktivní terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• antigeny CD274 MeSH
• antigeny CD279 MeSH
• B2M protein, human MeSH Prohlížeč
• beta-2-mikroglobulin MeSH
• CD274 protein, human MeSH Prohlížeč
• MHC antigeny II. třídy MeSH
• nivolumab MeSH
• PDCD1 protein, human MeSH Prohlížeč
• protinádorové látky imunologicky aktivní MeSH

The relationship between Epstein-Barr virus (EBV) and the germinal centre (GC) of the asymptomatic host remains an enigma. The occasional appearance of EBV-positive germinal centres in some patients, particularly those with a history of immunosuppression, suggests that EBV numbers in the GC are subject to immune control. The relationship, if any, between lymphoid hyperplasia with EBV-positive germinal centres and subsequent or concurrent lymphomagenesis remains to be clarified. As far as the development of EBV-associated Hodgkin's lymphoma is concerned, the suppression of virus replication, mediated by LMP1 on the one hand, and the loss of B-cell receptor signalling on the other, appears to be an important pathogenic mechanism. A further important emerging concept is that alterations in the microenvironment of the EBV-infected B-cell may be important for lymphomagenesis.

• MeSH
• B-lymfocyty imunologie   virologie   MeSH
• buněčná diferenciace imunologie   MeSH
• dospělí MeSH
• Hodgkinova nemoc imunologie   virologie   MeSH
• infekce virem Epsteina-Barrové virologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• proteiny virové matrix MeSH
• pseudolymfom virologie   MeSH
• receptory antigenů B-buněk imunologie   MeSH
• replikace viru imunologie   MeSH
• virus Epsteinův-Barrové imunologie   MeSH
• zárodečné centrum lymfatické uzliny imunologie   virologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• EBV-associated membrane antigen, Epstein-Barr virus MeSH Prohlížeč
• proteiny virové matrix MeSH
• receptory antigenů B-buněk MeSH