Kupffer cell calibration of T cell responses via VSIG4-CD5 interaction promotes tumor evasion.

T cells by rescuing them from activation-induced cell death. This bidirectional regulation favors the outgrowth of poorly immunogenic metastatic tumor clones and fosters an immune landscape that is unfavorable to T cells as metastatic liver cancer progresses. We also show that blockade of VSIG4-CD5 interaction using a nanoantibody to VSIG4 sensitizes liver metastases to anti-PD-L1 therapy, achieving synergistic efficacy in mice. These findings provide mechanistic insights into cancer immunoediting during liver metastasis and a possible approach for treating immunologically cold tumors.