RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
晚期非小细胞肺癌患者免疫治疗后疗效预测的免疫特征
英文原题：Immune signatures of patients with advanced non-small-cell lung cancer for efficacy prediction after immunotherapy.
查看英文原题
Immune signatures of patients with advanced non-small-cell lung cancer for efficacy prediction after immunotherapy.
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研究概要
NSCLC 中对 IO 的应答与特定耗竭 T 细胞的下降相关，提示 IO 可能通过减少循环耗竭 T 细胞来发挥治疗疗效，而循环耗竭 T 细胞与较差的生存相关，同时 IO 还可增加 TNF-α。这些结果凸显了监测循环耗竭 T 细胞变化以预测晚期肺癌 IO 应答和生存结局的预后价值。
研究思路结论见上方概要
背景
程序性细胞死亡蛋白1配体1（PD-L1）表达单独可能不是晚期非小细胞肺癌（NSCLC）免疫治疗（IO）疗效的最佳预测指标。使用质谱流式技术评估循环免疫特征是一种有前景的预测IO应答和预后的技术。循环免疫特征在晚期NSCLC中预测IO后疗效的效用仍有待阐明。
目的
评估循环免疫细胞和细胞因子在预测晚期NSCLC中IO治疗肿瘤反应方面的可行性。
方法
一项前瞻性观察性研究。为探究免疫特征的动态变化，前瞻性收集了NSCLC患者在基线时以及化疗（C/T）和/或IO后的血液标本。采用质谱流式细胞术和酶联免疫吸附试验来表征免疫特征和细胞因子模式，以识别免疫谱与治疗疗效之间的相关性。
结果
该研究入组了45例患者。单纯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。在单纯IO治疗有应答的患者中，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。单纯IO治疗后，肿瘤坏死因子-α（TNF-α）水平显著升高。单纯IO治疗前PD-1 + CD8 + T细胞高的患者，与低水平者相比，总生存期（OS）更短。化疗联合免疫治疗前LAG-3 + CD8 + T细胞高的患者，与低水平者相比，OS更短。
展开英文摘要原文
BACKGROUND
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.
OBJECTIVES
To assess the feasibility of circulating immune cells and cytokines in predicting tumor response to IO in advanced NSCLC. DESIGN: A prospective observational study.
METHODS
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.
RESULTS
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-1 + CD8 + T cells, PD-1 + CD4 + T cells, TIM-3 + CD8 + T cells, LAG-3 + NK cells, and LAG-3 + CD8 + 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-1 + CD8 + T cells before IO alone treatment had lower overall survival (OS) compared to those with low levels. Patients with high LAG-3 + CD8 + T cells before chemotherapy plus immunotherapy treatment had lower OS compared to those with low levels.
CONCLUSION
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.
论文信息
- 作者
- Luo YH、Shen CI、Chiang CL、Chen YM
- 第一作者单位
- Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.Taiwan
- 通讯作者单位
- Department of Chest Medicine, Taipei Veterans General Hospital, 201, Section 2, Shih-Pai Road, Taipei 11217, Taiwan.Taiwan
- 期刊
- Therapeutic advances in medical oncology2024
- 原文标识
- PubMed 39391353 · DOI 10.1177/17588359241284946
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