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Major Histocompatibility Complex Class II and Programmed Death Ligand 1 Expression Predict Outcome After Programmed Death 1 Blockade in Classic Hodgkin Lymphoma.
- Source :
-
Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2018 Apr 01; Vol. 36 (10), pp. 942-950. Date of Electronic Publication: 2018 Feb 02. - Publication Year :
- 2018
-
Abstract
- 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.
- Subjects :
- Antigen Presentation
Antineoplastic Agents, Immunological therapeutic use
B7-H1 Antigen antagonists & inhibitors
B7-H1 Antigen genetics
B7-H1 Antigen immunology
Chromosomes, Human, Pair 9
Cohort Studies
Histocompatibility Antigens Class II genetics
Histocompatibility Antigens Class II immunology
Hodgkin Disease genetics
Hodgkin Disease pathology
Humans
Predictive Value of Tests
Programmed Cell Death 1 Receptor biosynthesis
Programmed Cell Death 1 Receptor genetics
Programmed Cell Death 1 Receptor immunology
Progression-Free Survival
Reed-Sternberg Cells drug effects
Reed-Sternberg Cells immunology
Reed-Sternberg Cells pathology
Treatment Outcome
beta 2-Microglobulin biosynthesis
beta 2-Microglobulin genetics
beta 2-Microglobulin immunology
B7-H1 Antigen biosynthesis
Histocompatibility Antigens Class II biosynthesis
Hodgkin Disease drug therapy
Hodgkin Disease immunology
Nivolumab therapeutic use
Programmed Cell Death 1 Receptor antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1527-7755
- Volume :
- 36
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Journal of clinical oncology : official journal of the American Society of Clinical Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 29394125
- Full Text :
- https://doi.org/10.1200/JCO.2017.77.3994