放疗联合抗PD-1处理SCLC细胞对TAM、T细胞的免疫调控  

Mediated immunoregulation mechanism of TAM and dysfunctional T cells by radiotherapy combined with anti-PD-1 therapy in SCLC cells

作　　者：俞岑明[1] 崔晓佳[1] 谭程[1] 邰国梅[1] YU Cen-ming;CUI Xiao-jia;TAN Cheng;TAI Guo-mei(Department of Radiotherapy,Nantong Tumor Hospital,Nantong 226300,China)

机构地区：[1]南通市肿瘤医院放疗科,江苏南通226300

出　　处：《生物技术》2023年第4期500-507,共8页Biotechnology

基　　金：南通市卫生健康委员会科研课题(MB2021040)。

摘　　要：[目的]探讨小细胞肺癌(SCLC)细胞中放疗联合抗PD-1疗法调节TAM和功能失调性T细胞介导的免疫抑制。[方法]用4Gy的放疗剂量处理或不处理SCLC细胞系NCI-H209和NCI-H1688的肿瘤细胞条件培养基(CM)将巨噬细胞诱导为TAM,测定TAM的迁移能力。将T细胞与4Gy处理的肿瘤细胞CM培养诱导的TAM共培养后,测定T细胞增殖能力和T细胞杀伤力。比较放疗联合抗PD-1疗法与抗PD-1和吉非替尼疗法对吉非替尼抗性肿瘤细胞(NCI-H209-GR)CM培养的TAM、T细胞介导的免疫抑制。[结果]用4Gy处理的SCLC细胞的CM培养的TAM显示出较弱的迁移能力(233.49±22.09 vs 111.23±8.29,P<0.05)。4Gy和PD-L1抗体共处理的NCI-H209-GR细胞CM可显著抑制TAM迁移(169.76±17.77 vs 81.73±8.49,P<0.05),与4Gy和PD-L1抗体共处理的NCI-H209-GR细胞共培养的T细胞的增殖水平上升(82.79±0.95 vs 133.79±0.53,P<0.05)、T细胞杀伤力显著提高(81.12±10.80 vs 97.52±10.11,P<0.05)。[结论]SCLC细胞中放疗联合抗PD-L1疗法可协同抑制TAM迁移(169.76±17.77 vs 81.73±8.49),并增加功能失调性T细胞介导的溶细胞能力(81.12±10.80 vs 97.52±10.11)。[Objective]To investigate the regulation of TAM and dysfunctional T cell-mediated immunosuppression by radiotherapy combined with anti-PD-1 therapy in small cell lung cancer(SCLC)cells.[Method]Macrophages were induced to TAM by tumor cell conditioned medium(CM)with or without 4 Gy of radiotherapy dose treatment of SCLC cell lines NCI-H209 and NCI-H1688,and the migration ability of TAM was measured.After co-culture of T cells with TAM induced by CM culture of 4Gy-treated tumor cells,the T cell proliferation ability and T cell killing power were measured.To compare the TAM and T cell-mediated immunosuppression of gefitinib-resistant tumor cells(NCI-H209-GR)in CM culture by radiotherapy combined with anti-PD-1 therapy with anti-PD-1 and gefitinib therapy.[Result]CM-cultured TAM of SCLC cells treated with 4Gy showed weaker migration(233.49±22.09 vs 111.23±8.29,P0.05).CM of NCI-H209-GR cells co-treated with 4Gy and PD-L1 antibody significantly inhibited TAM migration(169.76±17.77 vs 81.73±8.49,P0.05),and the proliferation level of T cells co-cultured with NCI-H209-GR cells co-treated with 4Gy and PD-L1 antibodies increased(82.79±0.95 vs 133.79±0.53,P0.05),and T cell killing was significantly increased(81.12±10.80 vs 97.52±10.11,P0.05).[Conclusion]Radiotherapy combined with anti-PD-L1 therapy in SCLC cells synergistically inhibited TAM migration(169.76±17.77 vs 81.73±8.49)and increased dysfunctional T cell-mediated lytic capacity(81.12±10.80 vs 97.52±10.11).

关 键 词：小细胞肺癌 放疗 抗PD-L1疗法 TAM和 T细胞 

分 类 号：R734.2[医药卫生—肿瘤]