Intratumoral PD-1 CD8 T cells correlate with AFP levels in HCC patients: a brief report.

[PURPOSE] Hepatocellular carcinoma (HCC), the most common primary liver cancer, typically arises in a context of chronic inflammation driven by metabolic dysfunction, long-term alcohol use, viral hepatitis, and other etiologies. This study aimed to investigate whether intrahepatic and circulating immune profiles in HCC patients correlate with patient characteristics or clinical parameters.

[METHODS] Fresh tumor tissue, paired non-tumor liver tissue, and peripheral blood samples from 93 patients with HCC were analyzed using multiparametric flow cytometry to characterize lymphocyte subsets (T cells, NK cells, NKT cells, and B cells), immune checkpoint molecule expression (ICOS, 4-1BB, OX40, PD-1, TIM-3, LAG-3, and CTLA-4), and activation status. Associations between immune parameters and patient demographic or clinical features were assessed.

[RESULTS] Circulating alpha-fetoprotein (AFP) levels positively correlated with tumor-infiltrating PD-1high CD8+ T cell frequency (r=0.45, p<0.0001), but this correlation was not observed in non-tumoral or circulating compartments.

[CONCLUSION] AFP-producing HCC is linked to intra-tumoral immune exhaustion, marked by PD-1high CD8+ T cell accumulation, suggesting a localized immunosuppressive effect mediated by tumor-secreted AFP.

[SUPPLEMENTARY INFORMATION] The online version contains supplementary material available at 10.1007/s13402-026-01170-0.