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

## TL;DR

High PD-1 CD8+ T cells in liver tumors correlate with elevated AFP levels in liver cancer patients, indicating localized immune suppression.

## Contribution

Identifies a novel correlation between tumor-infiltrating PD-1high CD8+ T cells and AFP levels in hepatocellular carcinoma.

## Key findings

- Tumor-infiltrating PD-1high CD8+ T cell frequency correlates with circulating AFP levels (r=0.45, p<0.0001).
- This correlation is specific to tumor tissue and not observed in non-tumoral or circulating compartments.
- AFP-producing HCC is associated with immune exhaustion marked by PD-1high CD8+ T cell accumulation.

## Abstract

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.

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.

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.

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.

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