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Publication : PLCε1 suppresses tumor growth by regulating murine T cell mobilization.

First Author  Strazza M Year  2020
Journal  Clin Exp Immunol Volume  200
Issue  1 Pages  53-60
PubMed ID  31867717 Mgi Jnum  J:294352
Mgi Id  MGI:6451260 Doi  10.1111/cei.13409
Citation  Strazza M, et al. (2020) PLCepsilon1 suppresses tumor growth by regulating murine T cell mobilization. Clin Exp Immunol 200(1):53-60
abstractText  Phospholipase C epsilon 1 (PLCepsilon1) is a unique member of the phospholipase family, in that it also functions as a guanine nucleotide exchange factor (GEF) for the small GTPase Rap1. It is this function as a Rap1 GEF that gives PLCepsilon1 an essential role in chemokine-mediated T cell adhesion. We have utilized a syngeneic tumor model, MC38 cells in C57BL/6 mice, and observed that tumors grow larger and more quickly in the absence of PLCepsilon1. Single-cell analysis revealed an increased CD4(+) /CD8(+) ratio in the spleens, lymph nodes and tumors of PLCepsilon1 knock-out tumor-bearing mice. T cells isolated from PLCepsilon1 knock-out mice were less activated by multiple phenotypical parameters than those from wild-type mice. We additionally noted a decrease in expression of the chemokine receptors C-X-C chemokine receptor type 4 (CXCR4) and C-C motif chemokine receptor 4 (CCR4) on CD4(+) T cells from the spleens, lymph nodes and tumors of PLCepsilon1 knock-out mice compared to wild-type mice, and diminished migration of PLCepsilon1-depleted CD3(+) T cells towards stromal cell-derived factor (SDF)-1alpha. Based on these results, we conclude that PLCepsilon1 is a potential regulator of tumor-infiltrating lymphocytes, functioning, at least in part, at the level of T cell trafficking and recruitment.
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