晚期非小细胞肺癌淋巴细胞亚群及细胞因子与免疫疗效的关系研究

Study on the relationship between lymphocyte subsets,cytokines and immune efficacy in advanced non-small cell lung cancer

目的 免疫检查点抑制剂明显改变了非小细胞肺癌的治疗前景。PD-L1作为免疫治疗的生物标志物已广泛应用于临床,但仍存在部分缺陷,所以进一步研究血清相关标记物在临床中的预测效果是有必要的。方法 回顾性收集河南省人民医院2019年1月-2021年6月收治的接受免疫治疗的晚期非小细胞肺癌患者48例,并于治疗前及治疗4周期后抽取空腹外周血,检测其细胞因子及淋巴细胞亚群水平。4周期后依据疗效[完全缓解(CR)、部分缓解(PR)、疾病稳定(SD)、疾病进展(PD)]将其分为控制组(CR+PR+SD,36例)和无效组(PD,12例)。比较2组间治疗后淋巴细胞亚群及细胞因子水平变化及与疗效的关系。结果 免疫治疗4周期后控制组的淋巴细胞水平、总T淋巴细胞水平及CD4^(+)T淋巴细胞水平明显高于无效组[(1 648±564)μL vs.(1 098±581)μL;(1 121±388)μL vs.(651±368)μL;540(367,799)μL vs. 245(125,411)μL,均P<0.05]。其中T细胞计数水平与肿瘤进展呈负相关,且表达水平越高越能获得更好的无进展生存时间(PFS)。相反,细胞因子中IL-4及IL-6的高表达与肿瘤进展呈明显正相关,其表达水平越高PFS越差。结论 淋巴细胞亚群及细胞因子的表达水平与晚期非小细胞肺癌患者的疗效密切相关,可作为晚期非小细胞肺癌免疫治疗疗效的预测因素。

Objective Immuno-checkpoint inhibitors significantly change the treatment prospects for non-small cell lung cancer.PD-L1,as a biomarker of immunotherapy,is extensively used in clinical settings,but some defects remain in its application.This study aimed to further explore the predictive effect of serum-related markers in clinical practice.Methods We retrospectively collected 48 cases of advanced non-small cell lung cancer patients receiving immunotherapy in Henan Provincial People's Hospital from 2019 to June 2021.Fasting peripheral blood was taken before treatment and after 4 cycles of treatment to detect the levels of cytokines and lymphocyte subsets.After four cycles,according to the efficacy(complete response,CR;partial response,PR;stable disease,SD;progressive disease,PD),it was divided into a control group(CR+PR+SD)for a total of 36 cases and an ineffective group(PD)for 12 cases.The changes in level after treatment between the two groups and the relationship with efficacy were compared.Results After the four cycles of immunotherapy treatment,lymphocyte levels,total T lymphocyte levels,and CD4+T lymphocyte levels in the control group were significantly higher than those in the ineffective group[(1648±564)μL vs.(1098±581)μL;(1121±388)μL vs.(651±368)μL;540(367,799)μL vs.245(125,411)μL,all P<0.05].The count level of T cells was significantly negatively correlated with tumor progression,and a higher T cell expression level corresponded with better progression-free survival(PFS).Conversely,the high expression of IL-4 and IL-6 was significantly positively correlated with tumor progression,and PFS was worse.Conclusion The lymphocyte subgroups and expression levels of cytokines are closely related to the efficacy of patients with advanced non-small cell lung cancer.They can be used as predictors of the efficacy of immunotherapy for advanced non-small cell lung cancer.