淋巴细胞亚群及血浆细胞因子对广泛期小细胞肺癌免疫联合化疗预后及安全性的预测价值

Predictive value of lymphocyte subsets and plasma cytokines for prognosis and safety in extensive-stage small cell lung cancer treated with immunotherapy combined with chemotherapy

    摘要
  • 摘要:
    目的 探究外周血淋巴细胞亚群、血浆细胞因子对一线接受免疫检查点抑制剂（immune checkpoint inhibitor，ICI）联合化疗的广泛期小细胞肺癌（extensive-stage small cell lung cancer，ES-SCLC）有效性和安全性预测价值。
    方法 回顾性分析2020年10月至2024年12月于首都医科大学附属北京胸科医院接受ICI联合化疗的80例ES-SCLC患者资料。按照无进展生存期（progression-free survival，PFS）是否大于6个月、总生存期（overall survival，OS）是否大于13个月分为预后良好组和预后不良组。分析临床病理资料、淋巴细胞亚群及血浆细胞因子水平对患者预后、安全性的影响。
    结果 截至末次随访发生疾病进展78例，中位PFS为6个月；死亡59例，中位OS为13个月。预后良好：PFS≥6个月组46例（58.0%），OS≥13个月组40例（50.0%）；预后不良：PFS<6个月组34例（42.0%），OS<13个月组36例（45.0%）。PFS≥6个月患者的IL-17A、Th细胞百分比显著低于PFS<6个月组的患者（P=0.015，P=0.021）；OS≥13个月组的IL-17A显著低于OS<13个月组的患者（P=0.048）；总淋巴细胞百分比明显高于OS<13个月组的患者（P=0.002）。多因素Cox回归分析显示IL-17A、Th细胞百分比、总淋巴细胞百分比是独立预后因素。≥3级治疗相关不良事件（treatment-related adverse events，TRAEs）发生率为58.8%。总T细胞百分比及T细胞毒细胞百分比更高的患者，更易发生≥3级TRAEs（P=0.007，P=0.026）。
    结论 淋巴细胞亚群及血浆细胞因子与接受ICI联合化疗ES-SCLC患者的预后及TRAEs密切相关，旨在为临床治疗方案及干预措施的制定提供参考。

     

    Abstract:
    Objective We aimed to investigate the value of peripheral blood lymphocyte subsets and plasma cytokines in predicting the efficacy and safety of first-line immune checkpoint inhibitors (ICIs) plus chemotherapy in patients with extensive-stage small-cell lung cancer (ES-SCLC).
    Methods This retrospective study included 80 ES-SCLC patients who received ICIs plus chemotherapy at Beijing Chest Hospital, Capital Medical University, between October 2020 and December 2024. The patients were stratified into the favorable and poor prognosis groups according to whether their progression-free survival (PFS) exceeded 6 months and overall survival (OS) exceeded 13 months. The impact of the clinicopathological characteristics, counts of different lymphocyte subsets, and plasma cytokine levels on the prognosis and safety of ICIs in these patients were analyzed.
    Results At the final follow-up, 78 patients had experienced disease progression (median PFS, 6 months) and 59 patients died (median OS, 13 months). Further, 46 (58%) and 40 (50%) patients achieved a PFS ≥6 months and OS ≥13 months, respectively (favorable prognosis group); 34 (42%) and 36 (45%) patients achieved a PFS < 6 months and OS <13 months, respectively (poor prognosis group). Patients with a PFS ≥6 months exhibited significantly lower interleukin-17A (IL-17A) levels and lower T helper (Th) cell counts than those with a PFS < 6 months (P=0.015 and P=0.021, respectively). Patients with an OS ≥13 months exhibited significantly lower IL-17A levels (P=0.048) and significantly higher total lymphocyte counts (P=0.002) than those with an OS <13 months. Multivariate Cox regression analysis revealed that IL-17A levels and Th cell and total lymphocyte counts were independent prognostic factors in ES-SCLC patients receiving this treatment regimen. The incidence of grade ≥3 severe treatment-related adverse events (TRAEs) was 58.8%. Patients with higher total T cell and cytotoxic T cell counts were more likely to develop grade ≥3 TRAEs (P=0.007 and 0.026, respectively).
    Conclusions Peripheral blood lymphocyte subsets and plasma cytokines are closely correlated with the prognosis of, and TRAE occurrence in, ES-SCLC patients receiving ICIs plus chemotherapy. These biomarkers may aid the development of clinical treatment regimens and intervention strategies, thereby improving patient survival outcomes.

     

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