Luo Yung-Hung, Shen Chia-I, Chiang Chi-Lu, Chen Yuh-Min
Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Ther Adv Med Oncol. 2024 Oct 9;16:17588359241284946. doi: 10.1177/17588359241284946. eCollection 2024.
Programmed cell death protein 1 ligand 1 (PD-L1) expression alone may not be the optimal predictor of immunotherapy (IO) efficacy in advanced non-small cell lung cancer (NSCLC). Evaluation of circulating immune signatures using mass cytometry is a promising technique for predicting IO response and prognosis. The utility of circulating immune signatures for efficacy prediction after IO in advanced NSCLC remains to be elucidated.
To assess the feasibility of circulating immune cells and cytokines in predicting tumor response to IO in advanced NSCLC.
A prospective observational study.
To investigate dynamic changes in immune signatures, blood specimens were prospectively collected from patients with NSCLC at baseline and following chemotherapy (C/T) and/or IO. Mass cytometry and enzyme-linked immunosorbent assay were used to characterize immune signatures and cytokine patterns to identify correlations between immune profiles and treatment efficacy.
The study enrolled 45 patients. The proportion of circulating natural killer (NK) cells and CD8 T cells significantly increased after IO alone treatment. Cell levels of PD-1CD8 T cells, PD-1CD4 T cells, TIM-3CD8 T cells, LAG-3 NK cells, and LAG-3CD8 T cells significantly decreased in patients with treatment response to IO alone. Tumor necrosis factor-alpha (TNF-α) levels significantly increased after IO alone treatment. Patients with high PD-1CD8 T cells before IO alone treatment had lower overall survival (OS) compared to those with low levels. Patients with high LAG-3CD8 T cells before chemotherapy plus immunotherapy treatment had lower OS compared to those with low levels.
Responses to IO in NSCLC were correlated with declines in specific exhausted T cells, suggesting that IO may exert therapeutical efficacy by decreasing circulating exhausted T cells, which were associated with poorer survival, while also increasing TNF-α. These results highlight the prognostic value of monitoring changes in circulating exhausted T cells to predict IO response and survival outcomes in advanced lung cancer.
程序性细胞死亡蛋白1配体1（PD-L1）单独表达可能并非晚期非小细胞肺癌（NSCLC）免疫治疗（IO）疗效的最佳预测指标。利用质谱流式细胞术评估循环免疫特征是预测IO反应和预后的一项有前景的技术。循环免疫特征在晚期NSCLC接受IO治疗后对疗效预测的效用仍有待阐明。
评估循环免疫细胞和细胞因子在预测晚期NSCLC肿瘤对IO反应中的可行性。
一项前瞻性观察性研究。
为研究免疫特征的动态变化，前瞻性地收集了NSCLC患者在基线、化疗（C/T）和/或IO治疗后的血液标本。采用质谱流式细胞术和酶联免疫吸附测定法来表征免疫特征和细胞因子模式，以确定免疫谱与治疗疗效之间的相关性。
该研究纳入了45例患者。单独IO治疗后，循环自然杀伤（NK）细胞和CD8 T细胞的比例显著增加。单独IO治疗有反应的患者中，PD-1 CD8 T细胞、PD-1 CD4 T细胞、TIM-3 CD8 T细胞、LAG-3 NK细胞和LAG-3 CD8 T细胞的细胞水平显著降低。单独IO治疗后，肿瘤坏死因子-α（TNF-α）水平显著升高。单独IO治疗前PD-1 CD8 T细胞水平高的患者与水平低的患者相比，总生存期（OS）较短。化疗加免疫治疗前LAG-3 CD8 T细胞水平高的患者与水平低的患者相比，OS较短。
NSCLC对IO的反应与特定耗竭T细胞的减少相关，这表明IO可能通过减少循环中与较差生存相关的耗竭T细胞同时增加TNF-α来发挥治疗效果。这些结果突出了监测循环耗竭T细胞变化对预测晚期肺癌IO反应和生存结果的预后价值。
