弥漫性大B细胞淋巴瘤化疗后外周血T细胞亚群的动态变化

Dynamic Changes in Peripheral Blood T-Cell Subset after Immunochemotherapy Treatment in Diffuse Large B-Cell Lymphoma

摘要: 引言：弥漫性大B细胞淋巴瘤(Diffuse large B-cell lymphoma,DLBCL)患者体内T淋巴细胞亚群的转化和分布与疾病进展有关。CD4⁺T细胞亚群在体内启动和调节抗淋巴瘤免疫应答中的作用仍有争议。方法：我们回顾性分析了31例DLBCL患者的临床资料，他们接受了六个周期的一线治疗方案，即利妥昔单抗联合环磷酰胺、多柔比星、长春新碱和泼尼松龙(R-CHOP)。我们分别在诊断和治疗后收集了这些患者的外周血样本，循环淋巴细胞亚群的百分比由定量流式细胞术分析得出。结果：我们记录了Th1细胞的逐渐增加，这在T3时是显著的，Th2和Treg细胞的减少一直维持到R-CHOP治疗的T3时期。两个周期的治疗已经诱导Th1/Th2比率显著增长，并从那时起持续增加。我们发现基线和T3时Th1/Th2比值与达到完全缓解(Complete Response, CR)之间存在显著相关性。Th1细胞百分比与CR实现之间存在相关性，Th1细胞的临界值为43.09。结论：我们认为，在新诊断的患者中，R-CHOP可能通过抑制Th2的扩增来改变Th1/Th2比值的转化，这表明在治疗期间T细胞极化从促肿瘤T细胞应答强烈转变为抗肿瘤T细胞反应。

Abstract: Introduction: The transformation and distribution of specific T-cell subsets in diffuse large B-cell lymphoma (DLBCL) patients are connected with disease progression. The role of CD4⁺T cell subsets in initiating and regulating anti-lymphoma immune response in vivo remains controversial. Meth-ods: We retrospectively analyzed the clinical data of 31 patients diagnosed with DLBCL who under-went six cycles of rituximab-cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) chemotherapy or more, serving as the first-line therapy. We collected peripheral blood samples from these patients at diagnosis and post-treatment, and analyzed the percentages of circulating lymphocyte subsets by quantitative flow cytometry. Results: We documented a progressive in-crease of Th1 cells, which was significant at T3, and a decrease of Th2 and Treg cells which was maintained up to T3 of R-CHOP treatment. Two cycles of treatment have already induced significant growth in the Th1/Th2 ratio and maintained a progressive increase since then. We found a signifi-cant correlation between the level of Th1/Th2 ratio at baseline and T3, and the realization of the complete response (CR). There was a correlation between the percentage of Th1 cells and the reali-zation of the CR, with the cut-off value of 43.09 of Th1 cells. Conclusion: We believe that in newly di-agnosed patients, R-CHOP may change the transformation of Th1/Th2 ratio by inhibiting the ampli-fication of Th2. This analysis showed that the higher Th1/Th2 ratio and the increase of Th1 cells significantly correlated with the CR achievement, which suggests a strong transformation of T-cell polarization from a pro- to an anti-tumor T-cell response during treatment.