髓样肉瘤 (MS) 包括罕见的髓样肿瘤髓外表现，患者预后较差。虽然肿瘤微环境 (TME) 的临床相关性在许多恶性肿瘤中已得到充分证实，但 MS 中的信息有限。人类白细胞抗原 I 类 (HLA-I) 抗原的表达、HLA-I 抗原加工和呈递机制（通过免疫组织化学、多光谱成像和 RNA 测序 (RNAseq) 评估了来自两个独立队列的 45 个 MS 和配对骨髓 (BM) 样本的 APM）成分和 TME 组成。HLA-I 重链的显着下调（ HC；67.5%）和 ß2-微球蛋白（ß2M；64.8%），但与 BM 样本相比，MS 中发现 HLA-G 上调，这在公开数据集中得到了证实。此外，与配对的 BM (22.9%) 相比，MS 肿瘤显示主要免疫细胞排除 TME，组织浸润淋巴细胞 (TIL) 数量减少 (9.5%)。对 10 名 HLA-I HC 表达保留和减少的 MS 患者的子集进行 RNAseq 分析，发现有 150 个差异表达基因，并且在保留 HLA-I 表达的样本中发现炎症反应基因的表达显着减少。此外，多发性硬化症病例 TME 中的低 HLA-I 表达和低 TIL 数量与患者的预后较差有关。这项研究表明，免疫逃逸策略在多发性硬化症的发病机制和髓外扩散中普遍存在，这也发现于多发性硬化症的患者中。没有任何 BM 病理学证据的患者，这为开发针对多发性硬化症患者的新型个性化疗法提供了合理性。版权所有 © 2024 Bauer、Monecke、Hackl、Wilfer、Jaekel、Bläker、Al-Ali、Seliger 和 Wickenhauser。

Myeloid sarcomas (MS) comprise rare extramedullary manifestations of myeloid neoplasms with poor patients' outcome. While the clinical relevance of the tumor microenvironment (TME) is well established in many malignancies, there exists limited information in MS.The expression of the human leukocyte antigen class I (HLA-I) antigens, HLA-I antigen processing and presenting machinery (APM) components and the composition of the TME of 45 MS and paired bone marrow (BM) samples from two independent cohorts were assessed by immunohistochemistry, multispectral imaging, and RNA sequencing (RNAseq).A significant downregulation of the HLA-I heavy chain (HC; 67.5%) and ß2-microglobulin (ß2M; 64.8%), but an upregulation of HLA-G was found in MS compared to BM samples, which was confirmed in a publicly available dataset. Moreover, MS tumors showed a predominantly immune cell excluded TME with decreased numbers of tissue infiltrating lymphocytes (TILs) (9.5%) compared to paired BM (22.9%). RNAseq analysis of a subset of 10 MS patients with preserved and reduced HLA-I HC expression revealed 150 differentially expressed genes and a significantly reduced expression of inflammatory response genes was found in samples with preserved HLA-I expression. Furthermore, low HLA-I expression and low TIL numbers in the TME of MS cases were linked to an inferior patients' outcome.This study demonstrated a high prevalence of immune escape strategies in the pathogenesis and extramedullary spread of MS, which was also found in patients without evidence of any BM pathology, which yields the rational for the development of novel individually tailored therapies for MS patients.Copyright © 2024 Bauer, Monecke, Hackl, Wilfer, Jaekel, Bläker, Al-Ali, Seliger and Wickenhauser.