美国丹娜-法伯癌症研究所Margaret A. Shipp和X. Shirley Liu课题组合作揭示了经典型霍奇金淋巴瘤（cHLs）患者对PD-1封锁反应的外周免疫特征。相关论文于2020年8月10日发表于《自然-医学》杂志。

研究人员利用飞行时间分析作为T细胞受体（TCR）测序和细胞计数法的补充方法，获得了CheckMate 205 II期临床试验（NCT02181738）治疗的56例患者中他们对PD-1封锁反应的外周免疫特征。抗PD-1疗法在具有不同基线TCR库和在治疗期间相关单克隆扩增患者中最有效。在治疗过程中，CD4⁺而非CD8⁺，TCR多样性显著增加，尤其是在获得完全缓解的患者中。

另外，对治疗有反应的患者中活化的自然杀伤细胞和新近鉴定的CD3^-CD68⁺ CD4⁺ GrB⁺亚群数量增加。这些研究强调了在cHL患者中，新近扩增的、克隆多样性CD4⁺ T细胞和先天性效应物在PD-1封锁治疗中的作用。

据悉，PD-1封锁对治疗cHLs非常有效，在经典霍奇金淋巴瘤患者中，9p24.1染色体上的CD274（PD-L1）和PDC1LG2（PD-L2）经常出现拷贝数增加。然而，在这种MHC-I类阴性的肿瘤中，仍然不确定抗PD-1治疗的作用机制。

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