套细胞淋巴瘤 (MCL) 依赖于支持性肿瘤免疫微环境 (TIME)，其中 CD163 巨噬细胞的浸润会对预后产生负面影响。本研究探讨了 CD163 细胞的丰度和空间定位与 MCL TIME 生物学的关系。这是通过分别对肿瘤和浸润性 CD163 和 CD3 细胞进行空间多组学研究来实现的。我们分析了 100 名患者的诊断性 MCL 组织。通过 GeoMx® 组织微阵列数字空间分析测量了 63 种蛋白质。在肿瘤丰富和肿瘤稀疏的组织区域中选择感兴趣区域（ROI）。对 CD163 巨噬细胞片段、CD20 MCL 肿瘤细胞片段和 CD3 T 细胞片段进行了分子分析。为了验证蛋白质谱，在 CD20 细胞和两个 T 细胞亚群中测量了 1811 个 mRNA。使用图像分析来提取每个目标细胞的表型和位置，从而可以探索细胞频率和细胞邻域。蛋白质组学研究表明，CD163 细胞根据定位调节其免疫特征，并且免疫抑制分子 VISTA 和 B7-H3 在肿瘤稀疏的组织区域与肿瘤丰富的组织区域相比具有更高的表达，因此应该探索靶向作用。我们发现 CD163 细胞浸润更丰富的 MCL 组织具有更高的丝裂原激活蛋白激酶 (MAPK) 途径关键成分的表达，这一点通过互补 mRNA 分析得到了验证。因此，MAPK通路可能是CD163细胞浸润的MCL患者的可行治疗靶点。我们进一步展示了 CD11c 和 CD163 在既定风险因素之外的独立和综合预后价值。版权所有 © 2024 美国血液学会。

Mantle cell lymphoma (MCL) is dependent on a supportive tumor immune microenvironment (TIME), where infiltration of CD163+ macrophages has a negative prognostic impact. This study explores how abundance and spatial localization of CD163+ cells are associated with the biology of the MCL TIME. This is achieved through spatial multi-omic investigations of tumor and infiltrating CD163+ and CD3+ cells, respectively. We analyzed diagnostic MCL tissue from 100 patients. Sixty-three proteins were measured by GeoMx® digital spatial profiling in tissue microarrays. Regions of interests (ROIs) were selected in tumor-rich and tumor-sparse tissue regions. Molecular profiling of CD163+ macrophage segments, CD20+ MCL tumor cell segments and CD3+ T-cell segments was performed. To validate protein profiles, 1811 mRNAs were measured in CD20+ cells and two subsets of T-cells. Image analysis was used to extract the phenotype and position of each targeted cell allowing exploration of cell frequencies and cellular neighborhoods. Proteomic investigations revealed that CD163+ cells modulate their immune profile depending on the localization and that the immune inhibitory molecules VISTA and B7-H3 have higher expression in tumor-sparse versus tumor-rich tissue regions and targeting should be explored. We show that MCL tissues with more abundant infiltration of CD163+ cells have a higher expression of key components of the mitogen-activated protein kinase (MAPK) pathway, which was validated by complementary mRNA analyses. Thus, the MAPK pathway may be a feasible therapeutic target in MCL patients with CD163+ cell infiltration. We further show the independent and combined prognostic value of CD11c and CD163 beyond established risk factors.Copyright © 2024 American Society of Hematology.