Smeltzer Jacob P, Jones Jason M, Ziesmer Steven C, Grote Deanna M, Xiu Bing, Ristow Kay M, Yang Zhi Zhang, Nowakowski Grzegorz S, Feldman Andrew L, Cerhan James R, Novak Anne J, Ansell Stephen M
Authors' Affiliations: Division of Hematology; Division of Epidemiology; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota; and Department of Hematology, Tongji Hospital, Tongji University, Shanghai, China.
Authors' Affiliations: Division of Hematology; Division of Epidemiology; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota; and Department of Hematology, Tongji Hospital, Tongji University, Shanghai, China
Clin Cancer Res. 2014 Jun 1;20(11):2862-72. doi: 10.1158/1078-0432.CCR-13-2367. Epub 2014 Apr 11.
Transformation of follicular lymphoma is a critical event associated with a poor prognosis. The role of the tumor microenvironment in previous transformation studies has yielded conflicting results.
To define cell subtypes associated with transformation, we examined tissue specimens at diagnosis from patients with follicular lymphoma that later transformed and, using immunohistochemistry (IHC), stained for CD68, CD11c, CD21, CXCL13, FOXP3, PD1, and CD14. Cell content and the pattern of expression were evaluated. Those identified as significantly associated with time to transformation (TTT) and overall survival (OS) were further characterized by flow cytometry and multicolor IHC.
Of note, 58 patients were analyzed with median TTT of 4.7 years. The pattern of PD1(+) and CD14(+) cells rather than the quantity of cells was predictive of clinical outcomes. On multivariate analysis, including the follicular lymphoma international prognostic index score, CD14(+) cells localized in the follicle were associated with a shorter TTT (HR, 3.0; P = 0.004). PD1(+) cells with diffuse staining were associated with a shorter TTT (HR, 1.9; P = 0.045) and inferior OS (HR, 2.5; P = 0.012). Multicolor IHC and flow cytometry identified CD14(+) cells as follicular dendritic cells (FDC), whereas PD1(+) cells represented two separate populations, TFH and exhausted T cells.
These results identify the presence of PD1(+) T cells and CD14(+) FDC as independent predictors of transformation in follicular lymphoma. Clin Cancer Res; 20(11); 2862-72. ©2014 AACR.
滤泡性淋巴瘤转化是一个与预后不良相关的关键事件。肿瘤微环境在以往转化研究中的作用产生了相互矛盾的结果。
为了确定与转化相关的细胞亚型，我们检查了后来发生转化的滤泡性淋巴瘤患者诊断时的组织标本，并使用免疫组织化学（IHC）对CD68、CD11c、CD21、CXCL13、FOXP3、PD1和CD14进行染色。评估细胞含量和表达模式。通过流式细胞术和多色免疫组织化学进一步表征那些被确定与转化时间（TTT）和总生存期（OS）显著相关的细胞。
值得注意的是，对58例患者进行了分析，TTT中位数为4.7年。PD1(+)和CD14(+)细胞的模式而非细胞数量可预测临床结果。在多变量分析中，包括滤泡性淋巴瘤国际预后指数评分，位于滤泡中的CD14(+)细胞与较短的TTT相关（HR，3.0；P = 0.004）。弥漫性染色的PD1(+)细胞与较短的TTT相关（HR，1.9；P = 0.045）和较差的OS（HR，2.5；P = 0.012）。多色免疫组织化学和流式细胞术将CD14(+)细胞鉴定为滤泡树突状细胞（FDC），而PD1(+)细胞代表两个不同的群体，即滤泡辅助性T细胞（TFH）和耗竭性T细胞。
这些结果确定了PD1(+) T细胞和CD14(+) FDC的存在是滤泡性淋巴瘤转化的独立预测因素。《临床癌症研究》；20(11)；2862 - 2872。©2014美国癌症研究协会。
