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CD103 组织驻留记忆 T 细胞对预测食管癌免疫检查点抑制剂疗效的意义。

Significance of CD103 tissue-resident memory T cells for predicting the effectiveness of immune checkpoint inhibitors in esophageal cancer.

机构信息

Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-Machi, Abeno-Ku, Osaka, 545-8585, Japan.

Department of Gastroenterological Surgery, Fuchu Hospital, Osaka, Japan.

出版信息

BMC Cancer. 2023 Oct 20;23(1):1011. doi: 10.1186/s12885-023-11438-5.

Abstract

BACKGROUND

Immune checkpoint inhibitors (ICIs), including nivolumab, have been approved to treat esophageal cancer. However, these remedies are not fit for all patients with esophageal cancer; therefore, a predictive surrogate marker is needed to assess their effectiveness. CD103CD8 tumor-infiltrating lymphocytes, defined as tissue-resident memory T cells (T), are promising indicators of response to ICIs, but it remains to be elucidated. This study investigated the association between the efficacy of ICIs and T.

METHODS

The relationships between T infiltrating esophageal cancer, clinicopathological features, and prognosis after nivolumab initiation were examined using immunostaining. Tissue samples were obtained from surgically resected specimens of 37 patients with esophageal cancer who received nivolumab as a secondary or subsequent therapy. In addition, T infiltration was compared with programmed death-ligand 1 (PD-L1) expression and blood count parameters as predictors of nivolumab effectiveness.

RESULTS

T-rich patients had a significant survival benefit after nivolumab initiation (12-months overall survival 70.8% vs 37.2%, p = 0.0485; 12-months progression-free survival 31.2% vs 0%, p = 0.0153) and experienced immune-related adverse events more frequently than T-poor patients (6 vs 2 patients). T infiltration was weakly correlated with PD-L1 positivity (r = 0.374, p = 0.022), but T may indicate more sensitive response to ICIs than PD-L1 expression in this study. Some blood test parameters also weakly correlated with T but did not impact prognosis.

CONCLUSIONS

T-rich patients have a favorable prognosis after nivolumab initiation. Our results suggest that T are vital for antitumor immunity and are a promising predictor of ICIs effectiveness.

摘要

背景

免疫检查点抑制剂(ICI),包括纳武利尤单抗,已被批准用于治疗食管癌。然而,这些治疗方法并不适合所有食管癌患者;因此,需要一个预测性替代标志物来评估它们的疗效。CD103CD8 肿瘤浸润淋巴细胞,定义为组织驻留记忆 T 细胞(T),是对 ICI 反应的有希望的指标,但仍有待阐明。本研究探讨了 ICI 和 T 之间的疗效关系。

方法

使用免疫组化检查 T 浸润食管癌与临床病理特征的关系以及纳武利尤单抗起始后的预后。从 37 名接受纳武利尤单抗作为二线或后续治疗的食管癌患者的手术切除标本中获取组织样本。此外,将 T 浸润与程序性死亡配体 1(PD-L1)表达和血细胞计数参数作为纳武利尤单抗疗效的预测指标进行比较。

结果

T 丰富的患者在纳武利尤单抗起始后具有显著的生存获益(12 个月总生存率 70.8% vs 37.2%,p=0.0485;12 个月无进展生存率 31.2% vs 0%,p=0.0153),并且比 T 缺乏的患者更频繁地发生免疫相关不良事件(6 例 vs 2 例)。T 浸润与 PD-L1 阳性呈弱相关(r=0.374,p=0.022),但在本研究中,T 可能比 PD-L1 表达更能提示对 ICI 的敏感反应。一些血液检查参数也与 T 弱相关,但对预后没有影响。

结论

T 丰富的患者在纳武利尤单抗起始后具有良好的预后。我们的结果表明,T 对肿瘤免疫至关重要,是 ICI 疗效的有希望的预测指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6823/10588150/b499669341fe/12885_2023_11438_Fig1_HTML.jpg

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