HAVCR2 and cancer: In addition, TOOR et al. suggested that CD4 + lymphocytes in CRC tumor tissues are predominantly regulatory T cells (TREG) which can promote expression of immune checkpoints including cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), T cell immunoglobulin and mucin domain-3 (TIM-3), and lymphocyte-activated gene 3 (LAG-3), then further promote immune escape in cancer cells [36].