Chest Disease Department, University Hospital, 3 Boulevard Fleming, 25030, Besançon, France.
Methodology and Quality of Life in Oncology Unit, University Hospital, Besançon, France.
BMC Cancer. 2022 May 11;22(1):529. doi: 10.1186/s12885-022-09628-8.
BACKGROUND: There is a paucity of data regarding the prognostic influence of peripheral blood CD4+ T lymphopenia in non-small cell lung cancer (NSCLC). Therefore, we investigated the prognostic value of T lymphopenia in NSCLC. MATERIALS: Treatment-naive patients with a pathological diagnosis of NSCLC, at clinical stage I to IV were included in the prospective TELOCAP1 study. Lymphocytes count was evaluated in peripheral blood by flow cytometry. CD4+ and CD8+ T lymphopenia were defined as an absolute count of < 500/μL and < 224/μL respectively. The prognostic value of T lymphopenia was analyzed in the whole population, in local/loco-regional (stage I-IIIB) and in advanced (stage IV) NSCLC disease, using the Kaplan-Meier method and Cox regression models for survival curves and multivariate analysis, respectively. RESULTS: Between July 2010 and January 2014, 169 evaluable patients with clinical stage I to IV NSCLC were prospectively enrolled. The prevalence of CD4+ and CD8+ T lymphopenia was similar in the study population (around 29%). Patients with CD4+ T lymphopenia showed lower overall survival than those with CD4+ T lymphocytes count > 500/μL (median overall survival (OS) 16.1 versus 21.7 months, hazard ratio (HR): 1.616 [95% CI: 1.1-2.36], p = 0.012). This association with OS was especially marked in local/loco-regional NSCLC stages (median OS, 21.8 versus 72 months, respectively, HR: 1.88 [95% CI: 0.9-3.8], p = 0.035). Multivariate analysis confirmed the worse prognosis associated with CD4+ T lymphopenia in local/loco-regional NSCLC, but not in metastatic patients (HR 2.028 [95% CI = 1.065-3.817] p = 0.02). Restricted cubic spline analysis showed that patients with CD4+ T lymphocytes count ≤500/μL displayed a high risk of death regardless of NSCLC clinical stage. There was no obvious relationship between CD8+ T lymphopenia and clinical outcome. CONCLUSION: We identified CD4+ T lymphopenia as an independent prognostic factor in local/loco-regional stages of NSCLC and CD4+ T lymphopenia is also associated with a high risk of death, regardless of NSCLC clinical stage. TRIAL REGISTRATION: EUDRACT: 2009-A00642-55.
背景：关于外周血 CD4+T 淋巴细胞减少对非小细胞肺癌（NSCLC）的预后影响的数据很少。因此，我们研究了 T 淋巴细胞减少对 NSCLC 的预后价值。
材料：TELOCAP1 前瞻性研究纳入了临床分期 I 至 IV 期、经病理诊断为 NSCLC 且未经治疗的患者。通过流式细胞术评估外周血中的淋巴细胞计数。CD4+和 CD8+T 淋巴细胞减少分别定义为绝对计数 <500/μL 和 <224/μL。使用 Kaplan-Meier 方法和 Cox 回归模型进行生存曲线和多变量分析，分别分析 T 淋巴细胞减少在全人群、局部/局部区域（I-IIIB 期）和晚期（IV 期）NSCLC 中的预后价值。
结果：2010 年 7 月至 2014 年 1 月期间，前瞻性纳入了 169 例临床分期 I 至 IV 期 NSCLC 患者。研究人群中 CD4+和 CD8+T 淋巴细胞减少的发生率相似（约为 29%）。与 CD4+T 淋巴细胞计数>500/μL 的患者相比，CD4+T 淋巴细胞减少的患者总生存期更差（中位总生存期（OS）分别为 16.1 个月和 21.7 个月，风险比（HR）：1.616[95%CI：1.1-2.36]，p=0.012）。这种与 OS 的关联在局部/局部区域 NSCLC 分期中尤为明显（中位 OS 分别为 21.8 个月和 72 个月，HR：1.88[95%CI：0.9-3.8]，p=0.035）。多变量分析证实，在局部/局部区域 NSCLC 中，CD4+T 淋巴细胞减少与预后不良相关，但在转移性患者中则不然（HR 2.028[95%CI=1.065-3.817]，p=0.02）。限制性立方样条分析显示，无论 NSCLC 临床分期如何，CD4+T 淋巴细胞计数≤500/μL 的患者死亡风险均较高。CD8+T 淋巴细胞减少与临床结局之间没有明显关系。
结论：我们确定 CD4+T 淋巴细胞减少是局部/局部区域 NSCLC 分期的独立预后因素，且 CD4+T 淋巴细胞减少与 NSCLC 临床分期无关，与高死亡风险相关。
试验注册：EUDRACT：2009-A00642-55。
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