The development of immune checkpoint inhibitors (ICIs) has changed the therapeutic paradigm of lung cancer (LC), becoming the standard of treatment for previously untreated advanced non-small cell lung cancer (NSCLC) without actionable mutations. It has allowed the achievement of durable responses and resulted in significant survival benefits. However, not all patients respond; hence, molecular biomarkers are needed to help us predict which patients will respond. With this objective, a prospective observational study was designed, including a cohort of 55 patients with NSCLC who received ICIs. We studied whether biomarkers such as TCRβ and specific cytokines involved in the regulation of T cell activity were related to the immunotherapy response. In the survival analysis, it was found that patients with higher TCRβ clonality, lower TCRβ evenness, higher TCRβ Shannon diversity and lower TCRβ convergence had higher overall survival (OS) and progression-free survival (PFS). However, no statistically significant association was observed. Regarding cytokines, those patients with higher levels of IL-2 and IL-15 presented statistically significantly shorter OS and PFS, respectively. In fact, in the multivariable analysis, the high IL-15 level increased the risk of death by three times. Although the sample size was small and more studies are needed to confirm our results, our study reveals promising markers of responses to ICIs.
免疫检查点抑制剂（ICIs）的发展改变了肺癌（LC）的治疗模式，已成为无驱动基因突变的晚期非小细胞肺癌（NSCLC）一线治疗标准。该疗法能实现持久应答，并带来显著的生存获益。然而并非所有患者均能产生应答，因此需要分子标志物来预测潜在获益人群。基于此目标，本研究设计了一项前瞻性观察性研究，纳入55例接受ICIs治疗的NSCLC患者队列，探讨TCRβ及调控T细胞活性的特定细胞因子等生物标志物与免疫治疗应答的关联性。生存分析显示，具有较高TCRβ克隆性、较低TCRβ均匀度、较高TCRβ香农多样性及较低TCRβ趋同性的患者总生存期（OS）和无进展生存期（PFS）更优，但未达到统计学显著性。在细胞因子方面，IL-2与IL-15水平较高的患者分别呈现显著缩短的OS与PFS。多变量分析显示，高IL-15水平使死亡风险增加三倍。尽管样本量有限，仍需更多研究验证结果，但本研究揭示了具有潜力的ICIs应答预测标志物。
肿瘤(癌症)患者之家