A peripheral immune signature of responsiveness to PD-1 blockade in patients with classical Hodgkin lymphoma.

Autor: Cader FZ; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; AstraZeneca, City House, Cambridge, UK., Hu X; Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA, USA.; Harvard T.H. Chan School of Public Health, Boston, MA, USA.; GV20 Therapeutics LLC, Cambridge, MA, USA., Goh WL; Department of Cell Biology, Harvard Medical School, Boston, MA, USA., Wienand K; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Department of Hematology and Oncology, Göttingen Comprehensive Cancer Center, Göttingen, Germany., Ouyang J; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Mandato E; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Redd R; Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA, USA., Lawton LN; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Chen PH; Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Weirather JL; Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Schackmann RCJ; Department of Cell Biology, Harvard Medical School, Boston, MA, USA.; Merus, Utrecht, the Netherlands., Li B; Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA, USA.; Harvard T.H. Chan School of Public Health, Boston, MA, USA.; Lyda Hill Department of Bioinformatics, UT Southwestern Medical Center, Dallas, TX, USA., Ma W; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Clarion Healthcare, Boston, MA, USA., Armand P; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Rodig SJ; Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA., Neuberg D; Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA, USA., Liu XS; Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA, USA. xsliu@ds.dfci.harvard.edu.; Harvard T.H. Chan School of Public Health, Boston, MA, USA. xsliu@ds.dfci.harvard.edu., Shipp MA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Margaret_Shipp@dfci.harvard.edu.
Jazyk: angličtina
Zdroj: Nature medicine [Nat Med] 2020 Sep; Vol. 26 (9), pp. 1468-1479. Date of Electronic Publication: 2020 Aug 10.
DOI: 10.1038/s41591-020-1006-1
Abstrakt: PD-1 blockade is highly effective in classical Hodgkin lymphomas (cHLs), which exhibit frequent copy-number gains of CD274 (PD-L1) and PDC1LG2 (PD-L2) on chromosome 9p24.1. However, in this largely MHC-class-I-negative tumor, the mechanism of action of anti-PD-1 therapy remains undefined. We utilized the complementary approaches of T cell receptor (TCR) sequencing and cytometry by time-of-flight analysis to obtain a peripheral immune signature of responsiveness to PD-1 blockade in 56 patients treated in the CheckMate 205 phase II clinical trial (NCT02181738). Anti-PD-1 therapy was most effective in patients with a diverse baseline TCR repertoire and an associated expansion of singleton clones during treatment. CD4 + , but not CD8 + , TCR diversity significantly increased during therapy, most strikingly in patients who had achieved complete responses. Additionally, patients who responded to therapy had an increased abundance of activated natural killer cells and a newly identified CD3 - CD68 + CD4 + GrB + subset. These studies highlight the roles of recently expanded, clonally diverse CD4 + T cells and innate effectors in the efficacy of PD-1 blockade in cHL.
Databáze: MEDLINE
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