Potential Roles of Serum Exosomal CD155 and its Impact on NK Cell Immunosuppression in Hepatocellular Carcinoma.

BACKGROUND

Targeted therapies directed at tumor immune checkpoint, like programmed death-ligand (PD-L)1/programmed death (PD)-1, have shown remarkable progress. Nevertheless, treatment efficacy in hepatocellular carcinoma (HCC) is notably compromised due to the intricate immune microenvironment. Exploring alternative checkpoints beyond PD-L1/PD-1, including those not located on the cell surface, may improve our understanding of their roles in areas like diagnostic potential and immune tolerance in HCC.

AIMS

To explore the roles of serum exosomal CD155 (exo-CD155) in HCC.

STUDY DESIGN

Experimental study.

METHODS

We separated and analyzed serum exosomes from HCC patients. We quantified the concentrations of serum soluble CD155 (sCD155) and serum exo-CD155, and examined their association with disease progression, hepatitis B surface antigen (HBsAg) presence, and the concentrations of α-fetoprotein fraction L3 (AFP-L3) or alpha-fetoprotein (AFP). Additionally, we assessed the diagnostic effect through the receiver operating characteristic (ROC) curve, and the immune suppressive effect on natural killer (NK) cells of exo-CD155.

RESULTS

This study reveal elevated exo-CD155 levels in all HCC patients, with a significant increase in early-stage patients, exhibiting normal AFP/AFP-L3 or HBsAg-positive status. Exo-CD155 is linked to the progression of HCC and shows significant diagnostic effectiveness for the disease. Furthermore, the incubation of NK-92MI with exosomes derived from HCC patients leads to a substantial reduction in immune function, which can be partially counteracted with an antibody that blocks T cell immune receptor immunoglobulin and ITIM domains, (TIGIT)-blocking antibody.

CONCLUSION

These results disclose exo-CD155 shows promise for serving as a biomarker for HCC, especially in early-stage patients or those with normal AFP/AFP-L3 levels. Moreover, serum exosomes from HCC patients suppress NK cell immune functions through the TIGIT/CD155 pathway, contributing to immune tolerance in HCC.