Distinctive Subpopulations of Stromal Cells Are Present in Human Lymph Nodes Infiltrated with Melanoma
Distinctive Subpopulations of Stromal Cells Are Present in Human Lymph Nodes Infiltrated with Melanoma
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DOI：
10.1158/2326-6066.cir-19-0796
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发表时间：
2020-08-01
影响因子：
10.1
通讯作者：
Dunbar, P. Rod
中科院分区：
文献类型：
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作者：
Eom, Jennifer;Park, Saem Mul;Dunbar, P. Rod
人类肿瘤转移至淋巴结（LN）是一个普遍的负面预后因素。LN基质细胞（SC）在实现T细胞应答中起着至关重要的作用，并且由于肿瘤转移调节它们的结构和功能，这种相互作用可能抑制对肿瘤抗原的免疫应答。尚未确定对恶性细胞浸润到人淋巴结中有反应的SC亚群。在此，我们鉴定了黑色素瘤浸润淋巴结中存在的CD 90（+）SC的独特亚群，并将其与正常淋巴结中的相应亚群进行比较。第一群（CD 90（+）podoplanin（+）CD 105（+）CD 146（+）CD 271（+）VCAM-1（+）ICAM-1（+）α-SMA（+））对应于表达各种T细胞调节细胞因子、趋化因子和粘附分子的成纤维细胞网状细胞。第二种（CD 90（+）CD 34（+）CD 105（+）CD 271（+））代表了一种新的CD 34（+）SC群，它们包埋在胶原结构中，如囊和小梁，主要产生细胞外基质。我们还证明了这两个SC亚群与人LN周细胞的两个亚群不同，即高内皮微静脉和其他小血管壁中的CD 90（+）CD 146（+）CD 36（+）NG 2（-）周细胞，以及较大血管壁中的CD 90（+）CD 146（+）NG 2（+）CD 36（-）周细胞。区分人类淋巴结中的这些CD 90（+）SC亚群可以进一步研究它们各自对T细胞对肿瘤抗原的应答和临床结局的影响。
Metastasis of human tumors to lymph nodes (LN) is a universally negative prognostic factor. LN stromal cells (SC) play a crucial role in enabling T-cell responses, and because tumor metastases modulate their structure and function, this interaction may suppress immune responses to tumor antigens. The SC subpopulations that respond to infiltration of malignant cells into human LNs have not been defined. Here, we identify distinctive subpopulations of CD90(+) SCs present in melanoma-infiltrated LNs and compare them with their counterparts in normal LNs. The first population (CD90(+) podoplanin(+) CD105(+) CD146(+) CD271(+) VCAM-1(+) ICAM-1(+) alpha-SMA(+)) corresponds to fibroblastic reticular cells that express various T-cell modulating cytokines, chemokines, and adhesion molecules. The second (CD90(+) CD34(+) CD105(+) CD271(+)) represents a novel population of CD34(+) SCs embedded in collagenous structures, such as the capsule and trabeculae, that predominantly produce extracellular matrix. We also demonstrated that these two SC subpopulations are distinct from two subsets of human LN pericytes, CD90(+) CD146(+) CD36(+) NG2(-) pericytes in the walls of high endothelial venules and other small vessels, and CD90(+) CD146(+) NG2(+) CD36(-) pericytes in the walls of larger vessels. Distinguishing between these CD90(+) SC subpopulations in human LNs allows for further study of their respective impact on T-cell responses to tumor antigens and clinical outcomes.