科學家揭示PD1封鎖治療經典型霍奇金淋巴瘤患者的外周免疫特徵
作者：
小柯機器人發布時間：2020/8/11 18:57:00
美國丹娜-法伯癌症研究所Margaret A. Shipp和X. Shirley Liu課題組合作揭示了經典型霍奇金淋巴瘤（cHLs）患者對PD-1封鎖反應的外周免疫特徵。相關論文於2020年8月10日發表於《自然-醫學》雜誌。
研究人員利用飛行時間分析作為T細胞受體（TCR）測序和細胞計數法的補充方法，獲得了CheckMate 205 II期臨床試驗（NCT02181738）治療的56例患者中他們對PD-1封鎖反應的外周免疫特徵。抗PD-1療法在具有不同基線TCR庫和在治療期間相關單克隆擴增患者中最有效。在治療過程中，CD4+而非CD8+，TCR多樣性顯著增加，尤其是在獲得完全緩解的患者中。
另外，對治療有反應的患者中活化的自然殺傷細胞和新近鑑定的CD3-CD68+ CD4+ GrB+亞群數量增加。這些研究強調了在cHL患者中，新近擴增的、克隆多樣性CD4+ T細胞和先天性效應物在PD-1封鎖治療中的作用。
據悉，PD-1封鎖對治療cHLs非常有效，在經典霍奇金淋巴瘤患者中，9p24.1染色體上的CD274（PD-L1）和PDC1LG2（PD-L2）經常出現拷貝數增加。然而，在這種MHC-I類陰性的腫瘤中，仍然不確定抗PD-1治療的作用機制。
附：英文原文
Title: A peripheral immune signature of responsiveness to PD-1 blockade in patients with classical Hodgkin lymphoma
Author: Fathima Zumla Cader, Xihao Hu, Walter L. Goh, Kirsty Wienand, Jing Ouyang, Elisa Mandato, Robert Redd, Lee N. Lawton, Pei-Hsuan Chen, Jason L. Weirather, Ron C. J. Schackmann, Bo Li, Wenjiang Ma, Philippe Armand, Scott J. Rodig, Donna Neuberg, X. Shirley Liu, Margaret A. Shipp
Issue&Volume: 2020-08-10
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 CD3CD68+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.
DOI: 10.1038/s41591-020-1006-1
Source: https://www.nature.com/articles/s41591-020-1006-1