Abstract 218P
Background
Immunotherapy for hepatocellular carcinoma (HCC) has made remarkable progress in recent years, but the response rate has been limited. Recently, the presence of tumor-associated high endothelial venules (TA-HEV) around tumor tissues has been reported and may contribute to the response to immunotherapy. However, the clinical significance of TA-HEV in HCC is unknown, and we aimed to clarify the clinical significance of TA-HEV in HCC and its association with tumor-infiltrating lymphocytes (TIL).
Methods
Primary HCC patients who underwent radical resection were investigated (n=97). Double immunohistochemistry with anti-MECA-79 antibody and CD31 antibody was conducted to detect TA-HEV. In addition, we examined the association between CD8- and CD4-positive T-cell density and TA-HEV in the same patient group by immunohistochemistry. Next, TILs were analyzed by multicolor flow cytometry using tumor tissues from resected HCC cases (n=26) to examine the association between TIL subsets and TA-HEV.
Results
The patients were classified into 19 cases in the TA-HEV positive group and 78 cases in the TA-HEV negative group. There was no significant difference in the patient characteristics between the two groups. Prognostic analysis showed that DFS was significantly better in the TA-HEV positive group (Log-rank p=0.019), with 3-year DFS of 57.1% in the TA-HEV negative group and 89.2% in the TA-HEV positive group. The TA-HEV positive group had significantly higher intra-tumoral CD8-positive and CD4-positive T-cell densities assessed by immunohistochemistry (p=0.013, p=0.032, respectively). Multicolor flow cytometry was performed in 26 cases, 4 with TA-HEV and 22 without TA-HEV. In cases with TA-HEV, the ratio of T cells to total lymphocytes or effecter CD8-positive T cells (CD45RA-negative CD8-positive T cells) to total CD8-positive T cells was significantly higher than in cases without TA-HEV (p=0.013, p=0.002, respectively).
Conclusions
In HCC patients, DFS was significantly better in patients with TA-HEV. TILs showed a favorable trend for tumor immunity quantitatively and qualitatively in cases with TA-HEV, suggesting the possibility of TA-HEV-mediated immune activation in HCC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Osaka University.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.