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淋巴细胞亚群与晚期非小细胞肺癌免疫检查点抑制剂治疗疗效和预后的相关性:一项回顾性研究。

Association of lymphocyte subsets with efficacy and prognosis of immune checkpoint inhibitor therapy in advanced non-small cell lung carcinoma: a retrospective study.

机构信息

Department of Oncology, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.

出版信息

BMC Pulm Med. 2022 Apr 28;22(1):166. doi: 10.1186/s12890-022-01951-x.

Abstract

BACKGROUND

Immune checkpoint inhibitors (ICIs) have achieved promising effects in patients with non-small cell lung cancer (NSCLC). However, not all patients with NSCLC benefit from immunotherapy. There is an urgent need to explore biomarkers that could predict the survival outcomes and therapeutic efficacy in advanced NSCLC patients treated with immunotherapy. In this study, we aimed to assess the changes in peripheral blood lymphocyte subsets and their association with the therapeutic efficacy and clinical prognosis of advanced NSCLC patients treated with immunotherapy.

METHODS

A total of 276 patients with advanced NSCLC were enrolled. Peripheral blood lymphocyte subsets including CD4 T cells, CD8 T cells, CD4/CD8 ratio, NK cells, Tregs and B cells were collected before any treatment, before immunotherapy or chemotherapy, and after 4 cycles of immunotherapy or chemotherapy. T-test was used to analyze the factors influencing lymphocyte subsets and their changes before and after therapy. Logistic regression was used to plot ROC curves and analyze the relationship between lymphocyte subsets and therapeutic efficacy. Log-rank test and Cox regression model were used to evaluate the relationship between lymphocyte subsets and progression-free survival (PFS).

RESULTS

Gender, distant metastasis, and EGFR mutation status are known to affect the proportion of peripheral blood lymphocyte subsets in patients with advanced NSCLC. The proportions of CD4 T cells, CD8 T cells, Tregs and B cells were found to decrease after chemotherapy as compared to the baseline. The proportion of CD4 T cells, CD8 T cells, CD4/CD8 ratio, NK cells and Tregs were higher after immunotherapy than after chemotherapy. Compared to the baseline, the effective group showed significant increase in the proportions of CD4 T cells, CD4/CD8 ratio, NK cells and Tregs, and the number of CD8 T cells was significantly lower in the peripheral blood after 4 cycles of immunotherapy. On the contrary, the ineffective group did not show any significant differences in the above parameters. Baseline CD4 T cells and NK cells were independent predictors of immunotherapy efficacy and PFS. Baseline Tregs were independent predictor of immunotherapy efficacy.

CONCLUSION

Immune checkpoint inhibitors induced changes in the proportion of peripheral blood lymphocyte subsets in patients that responded well to immunotherapy. The levels of the different lymphocyte subsets could serve as valuable predictive biomarkers of efficacy and clinical prognosis for NSCLC patients treated with immunotherapy.

摘要

背景

免疫检查点抑制剂(ICIs)在非小细胞肺癌(NSCLC)患者中取得了令人瞩目的疗效。然而,并非所有 NSCLC 患者都能从免疫治疗中获益。因此,迫切需要探索生物标志物来预测接受免疫治疗的晚期 NSCLC 患者的生存结局和治疗效果。本研究旨在评估外周血淋巴细胞亚群的变化及其与免疫治疗晚期 NSCLC 患者治疗效果和临床预后的关系。

方法

共纳入 276 例晚期 NSCLC 患者。在开始任何治疗前、免疫治疗或化疗前以及免疫治疗或化疗 4 个周期后,采集外周血淋巴细胞亚群,包括 CD4 T 细胞、CD8 T 细胞、CD4/CD8 比值、NK 细胞、Tregs 和 B 细胞。采用 T 检验分析影响淋巴细胞亚群及其治疗前后变化的因素。采用逻辑回归绘制 ROC 曲线并分析淋巴细胞亚群与治疗效果的关系。采用 Log-rank 检验和 Cox 回归模型评估淋巴细胞亚群与无进展生存期(PFS)的关系。

结果

性别、远处转移和 EGFR 突变状态已知会影响晚期 NSCLC 患者外周血淋巴细胞亚群的比例。与基线相比,化疗后 CD4 T 细胞、CD8 T 细胞、Tregs 和 B 细胞的比例下降。与化疗相比,免疫治疗后 CD4 T 细胞、CD8 T 细胞、CD4/CD8 比值、NK 细胞和 Tregs 的比例升高。与基线相比,有效组 CD4 T 细胞、CD4/CD8 比值、NK 细胞和 Tregs 的比例显著升高,外周血中 CD8 T 细胞的数量在免疫治疗 4 个周期后显著降低。相反,无效组上述参数均无明显变化。基线 CD4 T 细胞和 NK 细胞是免疫治疗疗效和 PFS 的独立预测因子。基线 Tregs 是免疫治疗疗效的独立预测因子。

结论

免疫检查点抑制剂诱导了对免疫治疗反应良好的患者外周血淋巴细胞亚群比例的变化。不同淋巴细胞亚群的水平可以作为预测 NSCLC 患者免疫治疗疗效和临床预后的有价值的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7977/9052648/154957faf757/12890_2022_1951_Fig1_HTML.jpg

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