Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
Gastrointestinal Cancer Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
Asian Pac J Cancer Prev. 2022 Jul 1;23(7):2225-2231. doi: 10.31557/APJCP.2022.23.7.2225.
Blockade of immune checkpoint receptors in the treatment of cancers has been mentioned in several studies. Here, we investigated the efficacy of combined blockade of two inhibitory receptors, PD-1 and TIGIT, in restoring functional features of CD8+ T-cells in CLL.
CD8+ T-cells were separated from the peripheral blood of 11 CLL patients and targeted with malignant B-cells isolated from the same patients. Cells were then stimulated with anti-CD3/CD28 and PMA/ionomycin to assess their proliferative response and cytotoxic activity using MTT and CD107a degranulation assays, respectively. Cytokine production of isolated CD8+ T-cells was also determined using ELISA.
There were no significant differences in proliferation and cytotoxic activity of CD8+ T-cells co-blocked with anti-PD-1/TIGIT compared to those single blocked with anti-PD-1, anti-TIGIT, or the control antibody. There was no significant difference in cytokine production of mentioned groups, either.
Collectively, combined blockade of PD-1 and TIGIT failed to restore the proliferation and function of CD8+ T-cells isolated from CLL patients.
在几项研究中都提到了免疫检查点受体阻断在癌症治疗中的应用。在这里，我们研究了联合阻断两种抑制性受体 PD-1 和 TIGIT 对恢复 CLL 患者 CD8+ T 细胞功能特征的疗效。
从 11 名 CLL 患者的外周血中分离 CD8+ T 细胞，并与从同一患者中分离的恶性 B 细胞靶向。然后用抗 CD3/CD28 和 PMA/离子霉素刺激细胞，分别使用 MTT 和 CD107a 脱颗粒测定法评估其增殖反应和细胞毒性活性。还使用 ELISA 测定分离的 CD8+ T 细胞的细胞因子产生。
与单独阻断 PD-1、抗 TIGIT 或对照抗体相比，用抗 PD-1/TIGIT 联合阻断的 CD8+ T 细胞的增殖和细胞毒性活性没有显著差异。这些组的细胞因子产生也没有显著差异。
总之，联合阻断 PD-1 和 TIGIT 未能恢复从 CLL 患者中分离的 CD8+ T 细胞的增殖和功能。
