T cell inflammation profile after surgical resection may predict tumor recurrence in HBV-related hepatocellular...

The most effective treatment for HBV-related hepatocellular carcinoma (HCC) is surgical removal of the tumor in early stage patients. But many such patients will develop recurrent tumor within the first 24months, which is the major cause of death. To enable the prevention and earlier detection of recurrent HCC, we investigated the T cell responses that were potentially involved in HCC recurrence. We found that patients with recurrent HCC presented significantly lower frequencies of interferon gamma (IFNγ)-expressing Th1 cells and Tc1 cells, as well as significantly elevated Foxp3⁺ Treg cells, in the peripheral blood and the resected primary tumor. The peripheral blood and tumor-infiltrating T cells from patients with recurrent HCC also presented higher PD-1 and TIM-3 expression than patients without recurrent HCC. Interestingly, we observed a loss of IFNγ-expressing T cells and an increase in exhausted T cells in the peripheral blood after the removal of the HCC tumor. Furthermore, the T cell specificity in the HLA-A*02-positive patients in our cohort was examined. HBsAg-specific T cell responses could be observed in a subset of patients without HCC recurrence but not in patients with recurrent HCC, while NY-ESO-1-specific T cell responses were observed in a subset of both recurrent and non-recurrent groups. Together, these data indicated that HCC recurrence was associated with the type and robustness of T cell responses.