In addition, although two-thirds of CD8+ tumor infiltrating lymphocytes (TIL) express PD-1, one-third to half of CD8+ TIL are PD-1/CTLA-4 double-positive that exhibit more severe dysfunction than single-positive (PD-1+) TIL (Duraiswamy et al, 2013). Here, CTLA4 is linked to neoplasm.