Zhang Heng, Zheng Hui, Wang Yanchun, Chen Cuncun, Tong Ying, Xie Suhong, Ma Xiaolu, Guo Lin, Lu Renquan
Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China
J Immunother Cancer. 2025 Jan 11;13(1):e010026. doi: 10.1136/jitc-2024-010026.
Anti-programmed cell death protein 1 (anti-PD-1) antibodies have achieved revolutionary success in cancer therapy. However, the impact of anti-PD-1 therapy on host humoral immunity in humans during cancer immunotherapy requires further investigation.
We evaluated immunoglobulin titers by ELISA and screened the immune landscape of immune cells from 25 healthy donors and 50 cases including 25 new-onset hepatocellular carcinoma (HCC) patients prior to systemic treatment and 25 HCC patients undergoing anti-PD-1 therapy by multicolor flow cytometry. Flow or beads sorted cells were cultured ex vivo for proliferation and functional analysis.
Anti-PD-1 therapy significantly increased the levels of IgG and IgA in the periphery of HCC patients. Anti-PD-1 treatment led to an increase in plasmablasts and a notable rise in circulating T follicular regulatory (cTfr) cells, while changes in circulating B cells, T follicular helper cells, or regulatory T cells were not significant. Anti-PD-1 therapy also influenced the proliferation and function of cTfr cells, promoting the differentiation of CD38 cTfr cells. We observed that the CD38 Tfr cell subset in the peripheral blood can promote plasmablast differentiation, associated with altered antibody production.
Together, these data demonstrate the immunomodulatory role of PD-1 in restricting the differentiation and function of human cTfr cells and in regulating humoral immunity.
抗程序性细胞死亡蛋白1（抗PD-1）抗体在癌症治疗中取得了革命性的成功。然而，抗PD-1疗法在癌症免疫治疗期间对人体宿主体液免疫的影响仍需进一步研究。
我们通过ELISA评估免疫球蛋白滴度，并通过多色流式细胞术筛选了25名健康供者以及50例患者（包括25例全身治疗前的新发肝细胞癌（HCC）患者和25例接受抗PD-1治疗的HCC患者）的免疫细胞免疫格局。对通过流式或磁珠分选的细胞进行体外培养，以进行增殖和功能分析。
抗PD-1疗法显著提高了HCC患者外周血中IgG和IgA的水平。抗PD-1治疗导致成浆细胞增加，循环滤泡调节性T（cTfr）细胞显著增多，而循环B细胞、滤泡辅助性T细胞或调节性T细胞的变化不显著。抗PD-1疗法还影响cTfr细胞的增殖和功能，促进CD38+cTfr细胞的分化。我们观察到外周血中的CD38+Tfr细胞亚群可促进成浆细胞分化，这与抗体产生的改变有关。
总之，这些数据证明了PD-1在限制人类cTfr细胞的分化和功能以及调节体液免疫方面的免疫调节作用。
