非常规 T 细胞在泌尿系统肿瘤中：能抓住就抓住
Unconventional T cells in urological cancers: catch them if you can.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
低 CD8 T 细胞计数预测肌层浸润性膀胱癌患者从缺氧修饰治疗中获益
英文原题：Low CD8 T Cell Counts Predict Benefit from Hypoxia-Modifying Therapy in Muscle-Invasive Bladder Cancer.
查看英文原题
Low CD8 T Cell Counts Predict Benefit from Hypoxia-Modifying Therapy in Muscle-Invasive Bladder Cancer.
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研究概要
CD8+ T 细胞计数低的 MIBC 可能从缺氧修饰治疗中获益。
研究思路结论见上方概要
背景
由于缺氧可驱动免疫抑制性肿瘤微环境并抑制CD8+ T细胞，我们研究了肿瘤CD8+ T细胞低的患者是否能从缺氧修饰治疗中获益。
方法
BCON 是一项 III 期试验，将肌层浸润性膀胱癌（MIBC）患者随机分配至单纯放疗或联合缺氧修饰的 carbogen 加 nicotinamide（CON）治疗。对 116 例 BCON 患者的诊断性活检组织微阵列使用多重免疫组化（IHC）染色，标记物包括 CD8、CD4、FOXP3、CD68 和 PD-L1，以及 DAPI。使用 CA9 IHC 评估缺氧（n = 111）。关联的转录组数据（n = 80）用于识别分子亚型。使用 Cox 比例风险模型研究其与总生存期（OS）的关系。
结果
高（上四分位数）与低 CD8 T 细胞计数与整个队列 16 年时更好的 OS 相关（n = 116；HR 0.47，95% CI 0.28-0.78，p = 0.003），在单纯放疗组中也是如此（n = 61；HR 0.39，95% CI 0.19-0.76，p = 0.005）。CD8+ T 细胞低的患者从 CON 中获益（n = 87；HR 0.63，95% CI 0.4-1.0，p = 0.05），但 CD8 T 细胞高的患者未获益（n = 27；p = 0.95）。CA9 阳性肿瘤具有较少的 CD8+ T 细胞（p = 0.03）。在调整临床病理变量后，低 CD8+ T 细胞在整个队列中的预后意义仍然存在。基底型与管腔型相比具有更多的 CD8+ 细胞（p = 0.02），但并无预后意义（n = 80；p = 0.26）。使用其他免疫标志物的探索性分析未能在 CD8 计数所得结果的基础上进一步改善。
展开英文摘要原文
BACKGROUND
As hypoxia can drive an immunosuppressive tumour microenvironment and inhibit CD8+ T cells, we investigated if patients with low tumour CD8+ T cells benefitted from hypoxia-modifying therapy.
METHODS
BCON was a phase III trial that randomised patients with muscle-invasive bladder cancer (MIBC) to radiotherapy alone or with hypoxia-modifying carbogen plus nicotinamide (CON). Tissue microarrays of diagnostic biopsies from 116 BCON patients were stained using multiplex immunohistochemistry (IHC) with the markers CD8, CD4, FOXP3, CD68 and PD-L1, plus DAPI. Hypoxia was assessed using CA9 IHC ( n = 111). Linked transcriptomic data ( n = 80) identified molecular subtype. Relationships with overall survival (OS) were investigated using Cox proportional hazard models.
RESULTS
High (upper quartile) vs. low CD8 T cell counts associated with a better OS across the whole cohort at 16 years (n = 116; HR 0.47, 95% CI 0.28-0.78, p = 0.003) and also in the radiotherapy alone group ( n = 61; HR 0.39, 95% CI 0.19-0.76, p = 0.005). Patients with low CD8+ T cells benefited from CON ( n = 87; HR 0.63, 95% CI 0.4-1.0, p = 0.05), but those with high CD8 T cells did not ( n = 27; p = 0.95). CA9 positive tumours had fewer CD8+ T cells ( p = 0.03). Prognostic significance of low CD8+ T cells in the whole cohort remained after adjusting for clinicopathologic variables. Basal vs. luminal subtype had more CD8+ cells ( p = 0.02) but was not prognostic ( n = 80; p = 0.26). Exploratory analyses with other immune markers did not improve on findings obtained with CD8 counts.
CONCLUSIONS
MIBC with low CD8+ T cell counts may benefit from hypoxia-modifying treatment.
论文信息
- 作者
- Smith V、Mukherjee D、Tsakiroglou AM、Baker A、Mistry H、Choudhury A、Hoskin P、Illidge T
- 单位
- Division of Cancer Sciences, University of Manchester, Manchester M13 9PL, UK.United Kingdom
- 期刊
- Cancers2022 Dec 21
- 原文标识
- PubMed 36612036 · DOI 10.3390/cancers15010041
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