CTLA4 and neoplasm: Other observations related to LKB1 loss in the TME are: (1) increased numbers of Tregs; (2) the overexpression of T-cell inhibitory markers, such as PD-1, T-cell immunoglobulin mucin-3 (TIM-3), lymphocyte-activation gene 3 (LAG-3) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4); and (3) a reduction in tumor-infiltrating lymphocytes (TILs), which also exhibit elevated markers of T-cell exhaustion [28].