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

• MeSH
• adenokarcinom MeSH
• buněčné linie účinky léků   MeSH
• erbB receptory genetika   MeSH
• genová přestavba MeSH
• hybridizace in situ fluorescenční MeSH
• imunohistochemie MeSH
• klinické zkoušky jako téma MeSH
• lidé MeSH
• nemalobuněčný karcinom plic * diagnóza   genetika   MeSH
• onkogeny MeSH
• plošný screening MeSH
• randomizované kontrolované studie jako téma MeSH
• tyrosinkinasy antagonisté a inhibitory   MeSH
• Check Tag
• lidé MeSH