在利妥昔单抗时代,肿瘤微环境影响滤泡性淋巴瘤的生存及转化时间。
The tumour microenvironment influences survival and time to transformation in follicular lymphoma in the rituximab era.
作者信息
Blaker Yngvild Nuvin, Spetalen Signe, Brodtkorb Marianne, Lingjaerde Ole Christian, Beiske Klaus, Østenstad Bjørn, Sander Birgitta, Wahlin Björn Engelbrekt, Melen Christopher Michael, Myklebust June Helen, Holte Harald, Delabie Jan, Smeland Erlend Bremertun
机构信息
Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
出版信息
Br J Haematol. 2016 Oct;175(1):102-14. doi: 10.1111/bjh.14201. Epub 2016 Jun 24.
The tumour microenvironment influences outcome in patients with follicular lymphoma (FL), but its impact on transformation is less studied. We investigated the prognostic significance of the tumour microenvironment on transformation and survival in FL patients treated in the rituximab era. We examined diagnostic and transformed biopsies from 52 FL patients using antibodies against CD3, CD4, CD8, CD21 (CR2), CD57 (B3GAT1), CD68, FOXP3, TIA1, PD-1 (PDCD1), PD-L1 (CD274) and PAX5. Results were compared with a second cohort of 40 FL patients without signs of transformation during a minimum of five years observation time. Cell numbers and localization were semi-quantitatively assessed. Better developed CD21+ follicular dendritic cell (FDC) meshworks at diagnosis was a negative prognostic factor for overall survival (OS), progression-free survival (PFS) and time to transformation (TTT) in patients with subsequently transformed FL. Remnants of FDC meshworks at transformation were associated with shorter OS and PFS from transformation. High degrees of intrafollicular CD68+ and PD-L1+ macrophage infiltration, high total area scores and an extrafollicular/diffuse pattern of FOXP3+ T cells and high intrafollicular scores of CD4+ T cells at diagnosis were associated with shorter TTT. Scores of several T-cell subset markers from the combined patient cohorts were predictive for transformation, especially CD4 and CD57.
肿瘤微环境影响滤泡性淋巴瘤(FL)患者的预后,但对其向其他类型淋巴瘤转化的影响研究较少。我们调查了在利妥昔单抗时代接受治疗的FL患者中,肿瘤微环境对转化和生存的预后意义。我们使用抗CD3、CD4、CD8、CD21(CR2)、CD57(B3GAT1)、CD68、FOXP3、TIA1、PD-1(PDCD1)、PD-L1(CD274)和PAX5的抗体,检测了52例FL患者的诊断性活检和转化后的活检样本。将结果与另一组40例在至少5年观察期内无转化迹象的FL患者进行比较。对细胞数量和定位进行半定量评估。诊断时发育较好的CD21 +滤泡树突状细胞(FDC)网络,是随后发生转化的FL患者总生存期(OS)、无进展生存期(PFS)和转化时间(TTT)的不良预后因素。转化时FDC网络的残留与转化后的OS和PFS缩短有关。诊断时滤泡内CD68 +和PD-L1 +巨噬细胞高度浸润、总面积评分高、FOXP3 + T细胞的滤泡外/弥漫性模式以及CD4 + T细胞的滤泡内评分高与TTT缩短有关。来自合并患者队列的几个T细胞亚群标志物的评分可预测转化,尤其是CD4和CD57。