Aim: To explore the role of T cell immunoglobulin- and mucin- domain containing molecule-3 (Tim-3) in the induction of tumor immune tolerance by investigating the expression of two types of Tim-3 at the early stage of tumorigenesis and the temporal-spatial relationship between the expression of Tim-3 and other immuno-inhibitory genes in tumor.
Methods: By using semi-quantitative RT-PCR method, we investigated the expression of Tim-3, forkhead box P3 (Foxp3), cytotoxic T lymphocyte antigen 4 (CTLA-4), glucocorticoid-induced tumor necrosis factor receptor family-related receptor (GITR), TGF-beta, IL-10 and IFN-gamma at different time in tumor of tumor-bearing mice. Meanwhile, the growth of tumor was determined.
Results: At the early stage of tumorigenesis, sTim-3 was expressed before flTim-3 in tumor. When flTim-3 was expressed, the expression of sTim-3 was down-regulated. The expression of Foxp3, and GITR was simultaneous with that of flTim-3 and was up-regulated gradually with tumor growth. The expression of CTLA-4 was earlier than that of flTim-3 and also up-regulated gradually. The expression of flTim-3 and Foxp3 was also consistent with each other in tissue distribution. The growth of tumor was postively correlated with the expression of flTim-3, Foxp3, and CTLA-4 and negatively with the expression of sTim-3.
Conclusion: Along with the growth of tumor, immune tolerance was gradually established in tumor. flTim-3 but not sTim-3 may induce tumor immunological tolerance.