HHLA2 and hepatocellular carcinoma: Eyes absent homolog 2, which transcriptionally upregulates SOCS3 expression to block JAK-STAT signaling, was identified as a potential tumor suppressor in HCC and found to inhibit HCC progression.306 Conversely, CircSOD2 suppressed SOCS3 expression and triggered JAK2–STAT3 signaling to drive HCC progression.307 Furthermore, as a member of the B7 family of immune checkpoint proteins, HHLA2 was demonstrated to activate the JAK-STAT pathway and accelerate HCC progression by binding to TMIGD2.308