Novel expression of Neuropilin 1 on human tumor-infiltrating lymphocytes in colorectal cancer liver metastases
Novel expression of Neuropilin 1 on human tumor-infiltrating lymphocytes in colorectal cancer liver metastases
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DOI：
10.1517/14728222.2014.977784
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发表时间：
2015-02-01
影响因子：
5.8
通讯作者：
Elkord, Eyad
中科院分区：
文献类型：
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作者：
Chaudhary, Belal;Elkord, Eyad
目的：神经毡蛋白 1 (NRP1) 是一种跨膜蛋白，在生理和病理环境中具有多种作用。据报道，炎症微环境和次级淋巴组织中的 T 细胞表达 NRP1。肿瘤浸润淋巴细胞（TIL）在癌症预后中发挥着重要作用。在这项研究中，我们研究了来自结直肠癌肝转移 (LI/CRC) 的 TIL 和外周血单核细胞 (PBMC) 上的 NRP1 表达。方法：除了其他 Treg 相关标记物之外，还分析了来自 LI/CRC 的 TIL 以及来自健康供体和患者的 PBMC 的 NRP1 表达。将 PBMC 与肿瘤组织在体外共培养，并分析 NRP1 表达。结果：我们首次报道，与 PBMC 相比，NRP1 在 CD3(+)CD4(+) TIL 上高表达。 TIL 中 NRP1 表达与 CD25 表达密切相关。 NRP1 在表达 Helios(+) 和 Helios(-) FoxP3 的 Tregs 以及 FoxP3(-)Helios(-) T 细胞亚群上表达。在体外与肿瘤组织共培养后，它也在 PBMC 上被诱导。结论：NRP1 在 TIL 上上调，并且可以被肿瘤组织诱导到 PBMC 上。需要进一步研究来明确 NRP1 对人类 TIL 的功能。作为治疗靶点，NRP1 可能允许选择性靶向 TIL 亚群，包括抑制性 Tregs。
Objectives: Neuropilin 1 (NRP1) is a transmembrane protein with diverse roles in physiological and pathological settings. NRP1 expression has been reported on T cells in inflammatory microenvironments and in secondary lymphoid tissue. Tumor-infiltrating lymphocytes (TILs) play an important role in cancer prognosis. In this study, we investigated NRP1 expression on TILs and peripheral blood mononuclear cells (PBMCs) from colorectal cancer liver metastases (LI/CRC).Methods: TILs from LI/CRC and PBMCs from healthy donors and patients were analyzed for expression of NRP1, in addition to other Treg-related markers. PBMCs were co-cultured in vitro with tumor tissue and analyzed for NRP1 expression.Results: We report for the first time that NRP1 is highly expressed on CD3(+)CD4(+) TILs compared to PBMCs. NRP1 expression correlated closely with CD25 expression in TILs. NRP1 was expressed on both Helios(+) and Helios(-) FoxP3-expressing Tregs and on a FoxP3(-)Helios(-) T cell subset. It was also induced on PBMCs following in vitro co-culture with tumor tissue.Conclusions: NRP1 is upregulated on TILs and can be induced on PBMCs by tumor tissue. Further studies are warranted to define the function of NRP1 on human TILs. As a therapeutic target, NRP1 may allow selective targeting of TIL subsets including suppressive Tregs.