@article{c8cea5b0cbf044488c371c5a0a21587d,
title = "A peripheral immune signature of responsiveness to PD-1 blockade in patients with classical Hodgkin lymphoma",
abstract = "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.",
author = "Cader, {Fathima Zumla} and Xihao Hu and Goh, {Walter L.} and Kirsty Wienand and Jing Ouyang and Elisa Mandato and Robert Redd and Lawton, {Lee N.} and Chen, {Pei Hsuan} and Weirather, {Jason L.} and Schackmann, {Ron C.J.} and Bo Li and Wenjiang Ma and Philippe Armand and Rodig, {Scott J.} and Donna Neuberg and Liu, {X. Shirley} and Shipp, {Margaret A.}",
note = "Funding Information: After completing the current studies at DFCI, F.Z.C. and X.H. became full-time employees at Astra Zeneca and GV20, respectively. P.A. consults for Merck, Bristol Myers Squibb (BMS), Pfizer, Affimed, Adaptive, Infinity, ADC Therapeutics and Celgene and receives institutional research funding from Merck, BMS, Affimed, Adaptive, Roche, Tensha, Otsuka, Sigma Tau, Genentech and IGM and honoraria from Merck and BMS. S.J.R. has received research funding from BMS, Merck, Affimed and Kite/Gilead. X.S.L. is a cofounder and board member of GV20 Oncotherapy, SAB of 3DMedCare, consultant for Genentech, and stockholder of BMY, TMO, WBA, ABT, ABBV, and JNJ. X.S.L. has received funding from Takeda and Sanofi. M.A.S. has received research funding from BMS, Merck and Bayer and has served on advisory boards for BMS and Celgene. The remaining authors declare no competing financial interests. Publisher Copyright: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2020",
month = sep,
day = "1",
doi = "10.1038/s41591-020-1006-1",
language = "English (US)",
volume = "26",
pages = "1468--1479",
journal = "Nature Medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "9",
}