An intriguing but underexplored hypothesis is that induction of HLA class I-II molecules may lead to up-regulate immunoinhibitory molecules on tumor-infiltrating lymphocytes (TILs), such as lymphocyte activation gene 3 (LAG-3) that binds HLA class II and negatively regulates cellular proliferation, activation and homeostasis of T cells, in a similar fashion to CTLA-4 and PD-1. The gene discussed is CTLA4; the disease is neoplasm.