外周血检测指标联合TCF1^(+)CD8^(+)T淋巴细胞占比预测中晚期肺癌免疫治疗疗效及预后的临床队列研究

Peripheral Blood Laboratory Test Results Combined with TCF1^(+)CD8^(+)T Lymphocytes Ratio to Predict the Response and Prognosis of Immunotherapy to Advanced Lung Cancer

背景与目的免疫检查点抑制剂治疗目前缺乏可用于预测疗效的生物标志物,本研究旨在探讨外周血实验室检查指标联合淋巴细胞亚群分布与中晚期肺癌免疫治疗疗效及预后的相关性。方法前瞻性纳入2021年5月至2023年7月四川大学华西医院接受一线免疫治疗的中晚期肺癌患者,收集患者临床信息,同时采用流式细胞术检测患者治疗前后外周血淋巴细胞亚群。分别采用Logistic回归分析和Cox模型探究疗效和预后的影响因素。结果Logistic回归表明基线转录因子T细胞因子1(transcription factor T cell factor 1,TCF1)^(+)CD8^(+)T细胞占比及治疗1个周期后外周血白细胞计数、淋巴细胞百分比、细胞角蛋白19片段(cytokeratin 19 fragment,CYFRA21-1)水平、中性粒细胞淋巴细胞比率(neutrophil-lymphocyte ratio,NLR)是疗效的影响因素(P<0.05)。Cox回归分析显示基线TCF1^(+)CD8^(+)T细胞占比(P=0.020)、治疗1个周期后外周血白细胞计数(P<0.001)是预后的影响因素。结论基线高水平TCF1^(+)CD8^(+)T细胞占比和治疗1个周期后低水平白细胞计数和CYFRA21-1可能是患者从免疫治疗中获益的有利因素。

Background and objective Immune checkpoint inhibitors(ICIs)therapy lacks viable biomarkers for response and prognosis prediction.This study aimed to investigate the correlation of peripheral blood laboratory test results combined with lymphocyte subset ratios to the response and prognosis of immunotherapy in advanced lung cancer.Methods Advanced lung cancer patients admitted to West China Hospital,Sichuan University from May 2021 to July 2023 were prospectively enrolled in this study.Clinical data and peripheral blood were collected before and after treatment and lymphocyte subset ratios were analyzed by flow cytometry.Logistic regression was used to identify factors correlated to ICIs treatment efficacy.Cox modeling was applied to explore the prognostic factors.Results Logistic regression showed that the baseline level of transcription factor T cell factor 1(TCF1)^(+)CD8^(+)T cell ratio and peripheral white blood cell(WBC)count,lymphocyte percentage,cytokeratin 19 fragment(CYFRA21-1)after 1 cycle of ICIs treatment were the potential predictors for ICIs response(P<0.05).Cox regression analysis showed that the baseline level of TCF1^(+)CD8^(+)T cell ratio(P=0.020)and peripheral WBC count after 1 cycle of ICIs treatment(P<0.001)were prognostic factors.Conclusion Patients with high baseline TCF1^(+)CD8^(+)T cell ratio combined with low WBC counts and low CYFRA21-1 level after 1 cycle of ICIs treatment are more likely to benefit from ICIs therapy.