HAVCR2 and neoplasm: IL35 promotes tumorigenesis and tumor transendothelial extravasation by enhancing ICAM1 expression through the gp130- IL-12Rβ2 pathway [30,100] and also robustly induces multiple immune checkpoint molecules, such as PD1, T-cell immunoglobulin mucin 3 (TIM3, HAVCR2), lymphocyte-activation gene 3 (LAG3), and T-cell immunoreceptor with Ig and ITIM domains (TIGIT), in T cells and NK cells, resulting in immune exhaustion and dysfunction [100,101].