Novel expression of Neuropilin 1 on human tumor-infiltrating lymphocytes in colorectal cancer liver metastases

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.