文章：

缺乏滤泡内记忆CD4+ T细胞可预测新诊断滤泡性淋巴瘤的早期临床失败

Lack of intrafollicular memory CD4 + T cells is predictive of early clinical failure in newly diagnosed follicular lymphoma

原文发布日期：2021-07-15

DOI: 10.1038/s41408-021-00521-4

类型: Article

开放获取: 是

英文摘要：

Despite a characteristic indolent course, a substantial subset of follicular lymphoma (FL) patients has an early relapse with a poor outcome. Cells in the microenvironment may be a key contributor to treatment failure. We used a discovery and validation study design to identify microenvironmental determinants of early failure and then integrated these results into the FLIPI. In total, 496 newly diagnosed FL grade 1–3 A patients who were prospectively enrolled into the MER cohort from 2002 to 2012 were evaluated. Tissue microarrays were stained for CD4, CD8, FOXP3, CD32b, CD14, CD68, CD70, SIRP-α, TIM3, PD-1, and PD-L1. Early failure was defined as failing to achieve event-free survival at 24 months (EFS24) in immunochemotherapy-treated patients and EFS12 in all others. CyTOF and CODEX analysis were performed to characterize intratumoral immunophenotypes. Lack of intrafollicular CD4 expression was the only predictor of early failure that replicated with a pooled OR 2.37 (95%CI 1.48–3.79). We next developed a bio-clinical risk model (BioFLIPI), where lack of CD4 intrafollicular expression moved patients up one FLIPI risk group, adding a new fourth high-risk group. Compared with BioFLIPI score of 1, patients with a score of 2 (OR 2.17; 95% CI 1.08–4.69), 3 (OR 3.53; 95% CI 1.78–7.54), and 4 (OR 8.92; 95% CI 4.00–21.1) had increasing risk of early failure. The favorable intrafollicular CD4 T cells were identified as activated central memory T cells, whose prognostic value was independent from genetic features. In conclusion, lack of intrafollicular CD4 expression predicts early failure in FL and combined with FLIPI improves identification of high-risk patients; however, independent validation is warranted.
 

摘要翻译： 

尽管滤泡性淋巴瘤（FL）通常呈惰性病程，但仍有相当一部分患者会出现早期复发且预后不良。微环境中的细胞可能是治疗失败的关键因素。我们采用探索与验证研究设计，识别早期失败的微环境决定因素，并将这些结果整合至FLIPI评分系统中。本研究共评估了2002年至2012年间前瞻性纳入MER队列的496例新诊断FL 1-3A级患者。对组织芯片进行了CD4、CD8、FOXP3、CD32b、CD14、CD68、CD70、SIRP-α、TIM3、PD-1和PD-L1染色标记。早期失败定义为：接受免疫化疗治疗患者24个月内未达到无事件生存（EFS24），其他患者则为12个月内（EFS12）。研究采用CyTOF和CODEX分析技术来表征肿瘤内免疫表型特征。滤泡内CD4表达缺失是唯一可重复验证的早期失败预测因子，其汇总比值比（OR）为2.37（95%置信区间1.48-3.79）。随后我们开发生物临床风险模型（BioFLIPI），该模型将滤泡内CD4表达缺失作为风险升级因素——患者FLIPI风险组别相应提升一级，并新增第四高危组。与BioFLIPI评分1分者相比，评分2分（OR 2.17；95% CI 1.08-4.69）、3分（OR 3.53；95% CI 1.78-7.54）及4分（OR 8.92；95% CI 4.00-21.1）患者的早期失败风险逐级递增。研究鉴定出具有预后价值的滤泡内CD4阳性T细胞为活化中央记忆T细胞，其预后价值独立于遗传学特征。结论表明，滤泡内CD4表达缺失可预测FL早期治疗失败，与FLIPI联合应用能提升高危患者的识别效能，但仍有待独立验证。

原文链接：

Lack of intrafollicular memory CD4 + T cells is predictive of early clinical failure in newly diagnosed follicular lymphoma