Postoperative immunotherapy for patients with hepatocarcinoma using tumor-infiltrating lymphocytes

To explore a more effective immunotherapy for cancer by studying tumor-infiltrating lymphocytes (TIL) of patients with hepatocarcinoma.

TIL isolated from freshly resected tumors of 12 patients with hepatocarcinomas were activated, expanded and cultured in vitro by incubation with interleukin-2, and then infused to the patients. The TIL cytotoxicity and phenotype were determined by MTT and immunohistochemical ABC methods.

The average weight and number of cells of the tumor tissues for culture of TIL were 4.8 g and 5.8 x 10(7) respectively, and the median expansion time was 31.8 days in vitro. The maximal expansion achieved 1000 fold, and the mean amplification rate was 198.5 fold. Lymphokine-activated killer cell culture supernatant could stimulate TIL growth. Ten of 12 patients received immunotherapy of TIL. The number of cells infused reached 4 x 10(8)-1.1 x 10(10). In 3 cases of our series, TIL infusions were done through a drug pump with a catheter embedded in the hepatic artery. Eight patients whose primary hepatic carcinomas were resected completely were followed up for 16 months with only one case (12.5%) having recurrence. The recurrence rates of them at 6 and 12 months after tumor resection were remarkably lower than those of the patients who did not receive TIL infusion (19.4% and 41.6%, respectively). One patient whose tumor was not able to be removed received TIL infusion twice and local alcohol injection several times. He has been alive for 9 months.

TIL isolated from the tumors of patients with hepatocarcinoma can be activated and expanded in vitro. It demonstrated remarkably cytotoxic activity against tumor targets. TIL infusion is an effective immunotherapy for patients with hepatocarcinoma in reducing recurrence after operation.