Moreover, exhausted T-cells express inhibitory surface receptors as CTLA-4, PD-1, BTLA4, CD160, LAG-3, Tim-3 and VISTA [70–75] among these, CTLA-4 and PD-1 down-regulate the immune activity and are actually targeted to restore the anti-tumor immunity (Figure 1). The gene discussed is CTLA4; the disease is neoplasm.