Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) as an undetermined tool in tumor cells

In the tumor microenvironment, the function of T cells is a fate-changer for tumor progression. In the meantime, CD28 and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) are vital role players in the controlling activity of T cells as an activator and deactivator, respectively. In T cells in comparison to CD28, the molecular mechanism of CTLA-4 is unclear. In addition, despite the fact that most tumor cell types express CTLA-4, its role in tumor cells is not well understood and only few studies focused on the role of CTLA-4 signaling in tumor cells. It is illustrated that CTLA-4 signaling causes PD-L1 expression in tumor cells. However, numerous characteristics of CTLA-4 signaling in tumor cells are ambiguous and require to be described. In this article, we proposed that the CTLA-4 signaling during immunotherapy with anti-CTLA-4 antibodies may cause poor responses by patients. In addition, we attract attention to several fundamental questions regarding CTLA-4 signaling in tumor cells. Overall, the CTLA-4 signaling function and the related gaps about its role in tumor cells in the present review are challenged.