The alternative immune checkpoints such as PD-1, CTLA-4, T-cell immunoglobulin domain and mucin domain-3 (TIM-3), B- and T-lymphocyte-associated (BTLA), which were detected on cytotoxic CD8+ T cells with a gradual and continuous upregulation, impair the recognition and killing of tumor cells (70). This evidence concerns the gene CTLA4 and neoplasm.