Up-regulation of Core 1 Beta 1, 3-Galactosyltransferase Suppresses Osteosarcoma Growth with Induction of IFN-γ Secretion and Proliferation of CD8+ T Cells

作者：Tang, Lei; Fu, Cegang; Zhao, Hongwei; Wang, Bofei; Jia, Siyu; Chen, Haidan^*; Cai, Huili^*

来源：CURRENT CANCER DRUG TARGETS, 2023, 23(4): 265-277.

DOI：10.2174/1568009622666221010105701

• Core 1 beta 1 3-galactosyltransferase or T synthase
• T antigen
• osteosarcoma
• CD8(+) T cells
• immune regulation
• IFN-gamma cytokine

Aim Abnormal glycosylation often occurs in tumor cells. T-synthase (core 1 beta 1,3-galactosyltransferase, C1GALT1, or T-synthase) is a key enzyme involved in O-glycosylation. Although T-synthase is known to be important in human tumors, the effects of T-synthase and T-antigen on human tumor responses remain poorly defined.Methods In this study, a T-synthase-specific short hairpin RNA (shRNA) or T-synthase-specific eukaryotic expression vector(pcDNA3.1(+)) was transfected into murine Osteosarcoma LM8 cells to assess the effects of T-synthase on T cells and cytokines.Results The up-regulation of T-synthase promoted the proliferation of osteosarcoma cells in vitro, but it promoted the proliferation of tumor initially up to 2-3 weeks but showed significant growth inhibitory effect after 3 weeks post-implantation in vivo. Osteosarcoma cells with high T-synthase expression in vitro promoted the proliferation and inhibited the apoptosis of CD8(+) T cells. Further, T-synthase up-regulation promoted CD8(+) T-cell proliferation and the increased production of CD4(+) T cell-derived IFN-gamma cytokines to induce the increased tumor lethality of CTLs.Conclusion Our data suggest that high T-synthase expression inhibits tumor growth by improving the body's anti-tumor immunity. Therefore, using this characteristic to prepare tumor cell vaccines with high immunogenicity provides a new idea for clinical immunotherapy of osteosarcoma.

• 单位
  1; 6