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Potential Roles of Serum Exosomal CD155 and its Impact on NK Cell Immunosuppression in Hepatocellular Carcinoma
Wenzheng Han1, Jinrong Lv2, Mintuo Wang1
1The First Affiliated Hospital, Wannan Medical College, Anhui, China.
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.
Insights
Elevated exosomal CD155 (exo-CD155) in hepatocellular carcinoma (HCC) patients shows diagnostic potential, especially in early stages. Serum exosomes from HCC patients suppress natural killer (NK) cell function via the TIGIT/CD155 pathway, indicating immune tolerance.
Area of Science:
- Immunology
- Oncology
- Biochemistry
Background:
- Targeted therapies for tumor immune checkpoints like PD-L1/PD-1 have advanced cancer treatment.
- Hepatocellular carcinoma (HCC) treatment efficacy is limited by its complex immune microenvironment.
- Investigating alternative immune checkpoints beyond PD-L1/PD-1 is crucial for understanding HCC diagnostics and immune tolerance.
Purpose of the Study:
- To investigate the role of serum exosomal CD155 (exo-CD155) in hepatocellular carcinoma (HCC).
- To assess the diagnostic potential of exo-CD155 in HCC.
- To evaluate the impact of exo-CD155 on natural killer (NK) cell immune function in HCC.
Main Methods:
- Serum exosomes were isolated and analyzed from HCC patients.
- Concentrations of serum soluble CD155 (sCD155) and exo-CD155 were quantified.
- Associations with disease progression, HBsAg, AFP-L3, and AFP were examined.
- Diagnostic accuracy was assessed using ROC curves.
- Immune suppressive effects on NK cells were evaluated.
Main Results:
- Elevated exo-CD155 levels were observed in all HCC patients, with significant increases in early-stage disease.
- Exo-CD155 levels correlated with HCC progression and demonstrated significant diagnostic effectiveness.
- HCC patient-derived exosomes suppressed NK-92MI cell immune function, partially reversible by TIGIT-blocking antibodies.
Conclusions:
- Serum exo-CD155 shows promise as a biomarker for HCC, particularly in early-stage or normal AFP/AFP-L3 patients.
- HCC-derived exosomes suppress NK cell immunity through the TIGIT/CD155 pathway.
- This pathway contributes to immune tolerance in the HCC microenvironment.
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