本期文章：《自然—免疫学》：Online/在线发表

美国宾夕法尼亚大学E. John Wherry等研究人员合作发现，PD-1指导的免疫疗法改变对季节性流感疫苗的Tfh和体液免疫反应。相关论文于2022年7月28日在线发表在《自然—免疫学》杂志上。

据研究人员介绍，抗程序化死亡-1（anti-PD-1）免疫疗法可重振癌症患者的CD8 T细胞反应，但PD-1也被其他免疫细胞表达，包括参与生发中心反应的滤泡辅助CD4 T细胞（Tfh）。然而，关于抗PD-1免疫疗法对人类非癌症免疫反应的影响却知之甚少。

为了研究这个问题，研究人员揭示了抗PD-1免疫疗法对Tfh-B细胞轴响应不相关病毒抗原的影响。流感疫苗接种后，接受抗PD-1的成人亚群比未接受免疫治疗的成人有更强的循环Tfh反应。与对照组相比，PD-1通路阻断导致循环Tfh和应答B细胞中细胞增殖的转录特征增加。观察结果表明，在免疫治疗患者的一个亚群中，Tfh-B细胞和生发中心轴发生了潜在的变化。这些结果共同证明了抗PD-1疗法对流感疫苗反应的动态影响，并强调分析性疫苗接种是一种可能揭示潜在免疫易感性不良事件的方法。

附：英文原文

Title: PD-1 directed immunotherapy alters Tfh and humoral immune responses to seasonal influenza vaccine

Author: Herati, Ramin Sedaghat, Knorr, David A., Vella, Laura A., Silva, Luisa Victoria, Chilukuri, Lakshmi, Apostolidis, Sokratis A., Huang, Alexander C., Muselman, Alexander, Manne, Sasikanth, Kuthuru, Oliva, Staupe, Ryan P., Adamski, Sharon A., Kannan, Senthil, Kurupati, Raj K., Ertl, Hildegund C. J., Wong, Jeffrey L., Bournazos, Stylianos, McGettigan, Suzanne, Schuchter, Lynn M., Kotecha, Ritesh R., Funt, Samuel A., Voss, Martin H., Motzer, Robert J., Lee, Chung-Han, Bajorin, Dean F., Mitchell, Tara C., Ravetch, Jeffrey V., Wherry, E. John

Issue&Volume: 2022-07-28

Abstract: Anti-programmed death-1 (anti-PD-1) immunotherapy reinvigorates CD8 T cell responses in patients with cancer but PD-1 is also expressed by other immune cells, including follicular helper CD4 T cells (Tfh) which are involved in germinal centre responses. Little is known, however, about the effects of anti-PD-1 immunotherapy on noncancer immune responses in humans. To investigate this question, we examined the impact of anti-PD-1 immunotherapy on the Tfh–B cell axis responding to unrelated viral antigens. Following influenza vaccination, a subset of adults receiving anti-PD-1 had more robust circulating Tfh responses than adults not receiving immunotherapy. PD-1 pathway blockade resulted in transcriptional signatures of increased cellular proliferation in circulating Tfh and responding B cells compared with controls. These latter observations suggest an underlying change in the Tfh–B cell and germinal centre axis in a subset of immunotherapy patients. Together, these results demonstrate dynamic effects of anti-PD-1 therapy on influenza vaccine responses and highlight analytical vaccination as an approach that may reveal underlying immune predisposition to adverse events.

DOI: 10.1038/s41590-022-01274-3