Department of Hematology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, Guangdong, People's Republic of China.
Department of Hematology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510180, Guangdong Province, People's Republic of China.
J Cancer Res Clin Oncol. 2021 Mar;147(3):691-701. doi: 10.1007/s00432-020-03446-w. Epub 2021 Jan 2.
Some chemotherapy drugs have immunomodulatory effects on specific tumors. The potential of vincristine (VCR) in the R-CHOP regimen to act as both a chemotherapeutic and an immunomodulatory agent via PD-L1 in tumor cells remains unclear.
In vitro screening VCR showed that the IC50 value of VCR in the DLBCL cell lines was approximately 2 nM. Western blotting and q-PCR were used to detect the expression of PD-L1. The effect of VCR combined with PD-L1 mAb was tested in a co-culture system of LY-OCI-3 cells and peripheral blood mononuclear cells and in DLBCL xenograft mouse model. Flow cytometry was used to determine the proportion of T lymphocyte subsets. The effect of the STAT3 inhibitor nifuroxazide on VCR-induced PD-L1 expression was tested in LY-OCI-3 and SU-DHL-4 cells.
VCR upregulated PD-L1 protein and mRNA expression in various DLBCL cell lines. PD-L1 Ab combined with VCR significantly increased the proportion of CD8 + Granzyme B + , INF-γ + or TNF-α + CD3 + T cells. VCR + PD-L1 Ab inhibited tumor growth more effectively than VCR monotherapy, whereas PD-L1 Ab alone had no significant effect. Survival time did not differ significantly between the PD-L1 Ab group and the control group, whereas it was significantly longer in the VCR monotherapy and combination groups which showed more longer survival compared with the former. Nifuroxazide downregulated p-STAT3 and PD-L1 protein levels.
VCR upregulated PD-L1 expression in DLBCL cells partially by promoting the p-STAT3; VCR combined with PD-L1 Ab activated effector T cells and increased the antitumor immune response in vitro and in vivo.
一些化疗药物对特定肿瘤具有免疫调节作用。长春新碱（VCR）在 R-CHOP 方案中通过肿瘤细胞中的 PD-L1 发挥化疗和免疫调节作用的潜力尚不清楚。
体外筛选 VCR 显示，VCR 在弥漫性大 B 细胞淋巴瘤（DLBCL）细胞系中的 IC50 值约为 2nM。Western blot 和 q-PCR 用于检测 PD-L1 的表达。在 LY-OCI-3 细胞和外周血单核细胞共培养系统以及 DLBCL 异种移植小鼠模型中测试 VCR 与 PD-L1 mAb 的联合作用。流式细胞术用于确定 T 淋巴细胞亚群的比例。在 LY-OCI-3 和 SU-DHL-4 细胞中测试 STAT3 抑制剂硝唑脒对 VCR 诱导的 PD-L1 表达的影响。
VCR 上调了各种 DLBCL 细胞系中 PD-L1 蛋白和 mRNA 的表达。PD-L1 Ab 与 VCR 联合使用显著增加了 CD8+Granzyme B+、INF-γ+或 TNF-α+CD3+T 细胞的比例。VCR+PD-L1 Ab 比 VCR 单药治疗更有效地抑制肿瘤生长，而 PD-L1 Ab 单独使用则没有明显效果。PD-L1 Ab 组与对照组的生存时间无显著差异，但 VCR 单药治疗和联合治疗组的生存时间明显更长，与前两组相比，其生存时间更长。硝唑脒下调了 p-STAT3 和 PD-L1 蛋白水平。
VCR 通过促进 p-STAT3 部分上调了 DLBCL 细胞中的 PD-L1 表达；VCR 联合 PD-L1 Ab 在体外和体内激活效应 T 细胞并增强了抗肿瘤免疫反应。
