When we measured the simultaneous IR expression in PD1+ T cells with or without CD28, we observed a significant decline of cells lacking all four IRs (quadruple negative, QN) (IR-1) and an increase in terms of cells co-expressing the 4 IRs (quadruple positive, QP) (IR-16), with the transition from periphery to the tumor in both the subsets (Fig. 5C). This evidence concerns the gene NISCH and neoplasm.