Background: Small-cell lung cancer (SCLC) is an aggressive type of lung cancer, and several factors are currently used to predict poor outcomes, including performance status (PS), extensive-stage disease, male sex, advanced age, and elevated lactate dehydrogenase (LDH) levels. In this study, we aimed to explore the role of Tegs and inflammatory indices, such as CRP and NLR, in predicting response to immunotherapy.Methods: Fifty-one therapy-naïve ES-SCLC patients and ten healthy donors were enrolled. Peripheral blood mononuclear cells (PBMCs) were isolated and stained with fluorochrome-conjugated monoclonal antibodies. Multicolor flow cytometry was performed to determine the levels of CD8+T cells and CD4+Tregs, as well as their correlation with inflammatory indices and clinical outcomes.Results:ES-SCLC patients harbored higher percentages of CD8+Teffs (p= 0.005) and FOXP3+Tregs (p< 0.0001) in circulation before therapy compared with healthy donors. In addition, high levels of CD3+CD8+T effectors were associated with longer PFS (p= 0.018) and longer OS (p= 0.012) compared with patients bearing low levels, while Tregs were not found to be predictive. More importantly, a survival benefit was observed in ES-SCLC patients with a low Treg/Teff ratio, as longer OS was observed in those with high percentages of CD8+Teffs and low FOXP3+CTLA-4+Tregs (p= 0.014) compared with those bearing low CD8+Teffs and high FOXP3+CTLA-4+Tregs. A low Treg/Teff ratio was further associated with low eosinophil levels and a low NLR before treatment initiation.Conclusions: These findings suggest a novel, easily obtainable blood-based signature that may help predict response to ICIs in ES-SCLC patients.
背景：小细胞肺癌（SCLC）是一种侵袭性肺癌，目前预测其不良预后的因素包括体能状态（PS）、广泛期疾病、男性、高龄及乳酸脱氢酶（LDH）水平升高。本研究旨在探讨调节性T细胞（Tregs）及炎症指标（如C反应蛋白[CRP]和中性粒细胞与淋巴细胞比值[NLR]）在预测免疫治疗应答中的作用。
方法：纳入51例初治广泛期小细胞肺癌（ES-SCLC）患者和10名健康供者。分离外周血单个核细胞（PBMCs），使用荧光标记的单克隆抗体进行染色，并通过多色流式细胞术检测CD8⁺ T细胞和CD4⁺调节性T细胞（Tregs）水平，分析其与炎症指标及临床结局的相关性。
结果：与健康供者相比，ES-SCLC患者治疗前外周血中CD8⁺效应T细胞（p=0.005）和FOXP3⁺调节性T细胞（p<0.0001）百分比更高。此外，高水平CD3⁺CD8⁺效应T细胞患者较低水平患者具有更长的无进展生存期（PFS，p=0.018）和总生存期（OS，p=0.012），而调节性T细胞未显示预测价值。更重要的是，低Treg/Teff比值（即高CD8⁺效应T细胞与低FOXP3⁺CTLA-4⁺调节性T细胞组合）的ES-SCLC患者生存获益更显著（p=0.014），且治疗前低Treg/Teff比值与低嗜酸性粒细胞水平及低NLR相关。
结论：这些发现提示一种新型、易获取的血液标志物特征，可能有助于预测ES-SCLC患者对免疫检查点抑制剂（ICIs）的治疗应答。
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