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). Methods: 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. Results: 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. Conclusions: 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：目前关于高危骨髓增生异常综合征（HR-MDS）患者骨髓环钻活检中免疫细胞免疫组化特征的研究数据有限。方法：我们采用数字病理学技术，对64例接受5-氮杂胞苷治疗的HR-MDS患者的骨髓环钻活检样本中主要适应性免疫细胞群密度（细胞数/平方毫米）进行客观量化。研究聚焦于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细胞及CD138(+) 浆细胞，并评估淋巴聚集体的存在情况与数量。研究同时纳入20例“非MDS”患者作为对照组。结果：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细胞与Th细胞密度增加与5-氮杂胞苷（5-AZA）治疗反应呈正相关。较高的T细胞、Tc细胞、Th细胞及浆细胞密度，以及较低的B细胞、Tregs细胞密度和Tregs/T细胞比值，与总生存期延长相关。Tregs细胞、Tregs/T细胞比值、Tregs/Tc比值及浆细胞密度降低则与无白血病生存期改善相关。通过将原始IPSS-R评分与免疫细胞参数结合构建的改良IPSS-R（IPSS-R-I）评分系统，不仅提升了总生存期的预测效能，且使Cox模型计算的风险比增加了一倍。结论：骨髓免疫组化特征分析是一种高效且易于应用的工具，可用于探究骨髓免疫微环境在MDS发病机制及疾病进展中的潜在作用，同时揭示其与5-AZA治疗反应及临床预后的关联性。
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