Evaluation of cell mediated immunity in advanced pancreatic carcinoma before and after treatment with interleukin-2 (IL-2)

The administration of high doses of Interleukin-2 (IL-2) either alone or in combination with other cytokines demonstrated that immunologic manipulation is capable of mediating the regression of established cancer in humans. Thus, there is an urgent need to develop and evaluate the effect of treatment with IL-2 on immunological parameters and outcome of patients with inoperable pancreatic carcinoma.

Twenty-one patients with advanced pancreatic cancer were the subjects of this study and all patients were diagnosed as unresectable pancreatic carcinoma on a clinical, surgical, radiological and laboratory basis. The patients were classified as group I: 10 patients treated by IL-2, and group II: 11 non-treated patients. We used a novel method of intra-arterial therapy. Patients in group I were subjected to surgical exploration for assessing the inoperability and catheterization of the splenic artery, gastroduodenal artery and hepatic artery in patients with liver metastasis. The course of therapy that started 15 days after catheterization included the following for 10 days, lipiodol 2.5ml, 0.5ml urographin 58%, and IL-2 1ml. After 15 days of immunostimulation bolus injection of chemotherapy was given including, lipiodol 10ml, urographin 2ml, mitomycin C 0.2mg/kg, carboplatin 1.5mg/kg, farmorubicin 1mg/kg, 5-fluorouracil 10mg/kg, and leukovorin 1.5mg/kg. Forty-five days following locoregional chemotherapy, the same procedure was followed in the same sequence with 10 daily courses of locoregional immunotherapy.

The results showed that there is a 70% relief of pain in group I compared to 0% in group II. Also, there is an improvement in body weight in 50% of group I in comparison to group II. Tumor size was decreased in 70% of the cases in group I. The mean survival was 11.9+/-4.9 months in group I compared to 5.6+/-1.5 in group II (p<0.0008). A highly significant increase of CD3 (p<0.0001), CD4 (p<0.001), CD8 (p<0.0001), CD16 (p<0.001), CD14 (p<0.0001), NK cytotoxicity (p<0.0001), T cell cytotoxicity (p<0.001), ICAM-1 (p<0.001), TNFalpha (p=0.001) IL-2 (p<0.001), and IL-2R (p=0.001) was seen in group I patients compared to group II patients.

Immunotherapy is a new modality for treatment of pancreatic carcinoma. Local administration of therapy seems to be an attractive way for delivering the optimum concentration of IL-2 target tissues avoiding the toxic side effects associated with high dose systemic treatment.