Histological analysis of hepatocellular carcinoma treated by intraarterial combined immunochemotherapy

We have previously reported the efficacy of intraarterial combined immunochemotherapy for 24 patients with unresectable hepatocellular carcinoma. This therapy consists of recombinant interleukin-2, OK-432, adriamycin, cyclophosphamide, and famotidine. We observed a complete response (CR) in 4, partial response (PR) in 3, minor response (MR) in 7, no change (NC) in 7, and progressive disease (PD) in 3. The response rate (CR+PR+MR) was 58.3%. The overall 2-year survival rate was 52%. The present study was designed to analyze the phenotype of tumor infiltrating lymphocytes and apoptosis-related antigen (Ley and Fas antigen) expression in tumor cells.

The analysis of phenotype of tumor infiltrating lymphocytes and apoptosis-related antigen (Ley and Fas antigen) expression in tumor cells were performed by immunohistochemical stain using resected specimens.

Lymphocytes markedly infiltrated into the tumor lesions in treated patients compared with untreated patients. Phenotypes of tumor infiltrating lymphocytes were CD8+ and HLA-DR+. Ley-positive and Fas-positive tumor cells were observed as well. Furthermore, in the strong lymphocyte infiltrating area, the Fas antigen in tumor cells were strongly expressed.

In conclusion, the antitumor effect of intraarterial combined immunochemotherapy may be related with the activation of tumor infiltrating lymphocytes. These lymphocytes may kill tumor cells in an apoptotic fashion. Fas ligand expression of TILs should be determined in future.