Tsakiraki Zoi, Spathis Aris, Bouchla Anthi, Pouliakis Abraham, Vryttia Pinelopi, Panayiotides Ioannis G, Pappa Vasiliki, Papageorgiou Sotiris G, Foukas Periklis G
2nd Department of Pathology, National and Kapodistrian University of Athens, Attikon University Hospital, 12462 Athens, Greece.
Hematology Unit, 2nd Department of Internal Medicine, National and Kapodistrian University of Athens, Attikon University Hospital, 12462 Athens, Greece.
Cancers (Basel). 2025 Mar 25;17(7):1104. doi: 10.3390/cancers17071104.
BACKGROUND/OBJECTIVES: There are limited data regarding immunohistochemical profiling of immune cells in bone marrow trephine biopsies of patients with high-risk myelodysplastic syndromes (HR-MDS).
We sought to objectively quantify, with the use of digital pathology, the density (cells/mm2) of the prominent adaptive immunity cell populations in sixty-four (64) bone marrow trephine biopsies of HR-MDS patients receiving 5-Azacytidine. We focused on CD3(+) T cells, CD8(+) cytotoxic T cells (Tc), helper T cells (Th), Foxp3(+) regulatory T cells (Tregs), CD20(+) B-cells and CD138(+) plasma cells and evaluated the presence and the number of lymphoid aggregates. A control group of twenty "non-MDS" patients was included in the study.
We identified a significant decrease in adaptive immune cell densities in the HR-MDS patients compared to the non-MDS controls. Increased T and Th cell densities correlated with the response to 5-Azacytidine (5-AZA) treatment. Higher T, Tc, Th and plasma cells densities and low B, Tregs and Tregs/T cells ratios correlated with increased overall survival. Reduced Tregs, Tregs/T cells, Tregs/Tc and plasma cells showed improved leukemia-free survival. A modified IPSS-R (IPSS-R-I), combining the initial IPSS-R with the immune populations' parameters, improved overall survival and showed a double-fold increase in Cox calculated hazard ratios.
Immunohistochemical bone marrow immune profiling represents a powerful and easily useable tool for investigating the possible role of bone marrow immune microenvironment in the pathogenesis and progression of MDS, but also its association with the response to 5-AZA treatment and clinical outcomes.
背景/目的：关于高危骨髓增生异常综合征（HR-MDS）患者骨髓活检组织中免疫细胞免疫组化分析的数据有限。
我们试图利用数字病理学客观量化64例接受5-氮杂胞苷治疗的HR-MDS患者骨髓活检组织中主要适应性免疫细胞群的密度（细胞/mm²）。我们重点关注CD3(+) T细胞、CD8(+) 细胞毒性T细胞（Tc）、辅助性T细胞（Th）、Foxp3(+) 调节性T细胞（Tregs）、CD20(+) B细胞和CD138(+) 浆细胞，并评估淋巴聚集物的存在和数量。研究纳入了20例“非MDS”患者作为对照组。
我们发现与非MDS对照组相比，HR-MDS患者的适应性免疫细胞密度显著降低。T细胞和Th细胞密度增加与对5-氮杂胞苷（5-AZA）治疗的反应相关。较高的T细胞、Tc细胞、Th细胞和浆细胞密度以及较低的B细胞、Tregs细胞和Tregs/T细胞比值与总生存期延长相关。Tregs细胞、Tregs/T细胞、Tregs/Tc细胞和浆细胞减少表明无白血病生存期改善。一种改良的国际预后评分系统（IPSS-R），将初始IPSS-R与免疫细胞群参数相结合，改善了总生存期，并使Cox计算的风险比增加了两倍。
免疫组化骨髓免疫分析是一种强大且易于使用的工具，可用于研究骨髓免疫微环境在MDS发病机制和进展中的可能作用，以及其与对5-AZA治疗反应和临床结局的关联。
