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滤泡性淋巴瘤中 CD8+FOXP3+与 CD4+CD8+细胞的滤泡间空间高共定位预示着良好的预后。

High inter-follicular spatial co-localization of CD8+FOXP3+ with CD4+CD8+ cells predicts favorable outcome in follicular lymphoma.

机构信息

Centre for Evolution and Cancer and Division of Molecular Pathology, The Institute of Cancer Research, London, UK.

Cancer Institute, University College London, London, UK.

出版信息

Hematol Oncol. 2022 Oct;40(4):541-553. doi: 10.1002/hon.3003. Epub 2022 Apr 28.

DOI:10.1002/hon.3003
PMID:35451108
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10577604/
Abstract

The spatial architecture of the lymphoid tissue in follicular lymphoma (FL) presents unique challenges to studying its immune microenvironment. We investigated the spatial interplay of T cells, macrophages, myeloid cells and natural killer T cells using multispectral immunofluorescence images of diagnostic biopsies of 32 patients. A deep learning-based image analysis pipeline was tailored to the needs of follicular lymphoma spatial histology research, enabling the identification of different immune cells within and outside neoplastic follicles. We analyzed the density and spatial co-localization of immune cells in the inter-follicular and intra-follicular regions of follicular lymphoma. Low inter-follicular density of CD8+FOXP3+ cells and co-localization of CD8+FOXP3+ with CD4+CD8+ cells were significantly associated with relapse (p = 0.0057 and p = 0.0019, respectively) and shorter time to progression after first-line treatment (Logrank p = 0.0097 and log-rank p = 0.0093, respectively). A low inter-follicular density of CD8+FOXP3+ cells is associated with increased risk of relapse independent of follicular lymphoma international prognostic index (FLIPI) (p = 0.038, Hazard ratio (HR) = 0.42 [0.19, 0.95], but not independent of co-localization of CD8+FOXP3+ with CD4+CD8+ cells (p = 0.43). Co-localization of CD8+FOXP3+ with CD4+CD8+ cells is predictors of time to relapse independent of the FLIPI score and density of CD8+FOXP3+ cells (p = 0.027, HR = 0.0019 [7.19 × 10 , 0.49], This suggests a potential role of inter-follicular CD8+FOXP3+ and CD4+CD8+ cells in the disease progression of FL, warranting further validation on larger patient cohorts.

摘要

滤泡性淋巴瘤（FL）淋巴组织的空间结构对研究其免疫微环境提出了独特的挑战。我们使用 32 名患者的诊断性活检的多光谱免疫荧光图像，研究了 T 细胞、巨噬细胞、髓样细胞和自然杀伤 T 细胞之间的空间相互作用。我们根据滤泡性淋巴瘤空间组织学研究的需要，定制了基于深度学习的图像分析管道，能够识别肿瘤滤泡内外的不同免疫细胞。我们分析了滤泡性淋巴瘤的滤泡间和滤泡内区域中免疫细胞的密度和空间共定位。滤泡间 CD8+FOXP3+细胞密度低，CD8+FOXP3+与 CD4+CD8+细胞共定位与复发（p=0.0057 和 p=0.0019）和一线治疗后进展时间较短（对数秩检验 p=0.0097 和对数秩检验 p=0.0093）显著相关。滤泡间 CD8+FOXP3+细胞密度低与复发风险增加相关，与滤泡性淋巴瘤国际预后指数（FLIPI）无关（p=0.038，风险比（HR）=0.42 [0.19，0.95]），但与 CD8+FOXP3+与 CD4+CD8+细胞共定位无关（p=0.43）。CD8+FOXP3+与 CD4+CD8+细胞共定位是复发时间的独立预测因子，与 FLIPI 评分和 CD8+FOXP3+细胞密度无关（p=0.027，HR=0.0019 [7.19×10-5，0.49]）。这表明滤泡间 CD8+FOXP3+和 CD4+CD8+细胞可能在 FL 的疾病进展中发挥作用，需要在更大的患者队列中进一步验证。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb9/10577604/2418f8aaf97b/HON-40-541-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb9/10577604/b9c935e9e0a3/HON-40-541-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb9/10577604/a0651e51b136/HON-40-541-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb9/10577604/0da92c31f980/HON-40-541-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb9/10577604/aab56dacb6fb/HON-40-541-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb9/10577604/8e39c9a274c1/HON-40-541-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb9/10577604/2418f8aaf97b/HON-40-541-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb9/10577604/b9c935e9e0a3/HON-40-541-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb9/10577604/a0651e51b136/HON-40-541-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb9/10577604/0da92c31f980/HON-40-541-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb9/10577604/aab56dacb6fb/HON-40-541-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb9/10577604/8e39c9a274c1/HON-40-541-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb9/10577604/2418f8aaf97b/HON-40-541-g005.jpg

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