Pancreatic Cancer and Immunosuppression: Effects of Interleukin-2 on T-Lymphocytes Subpopulations in the Perioperative Period

Degrate L, Nobili C, Perego E, Franciosi C, Caprotti R, Romano F, Uggeri Fr

Department of Surgery, San Gerardo Hospital, University of Milano-Bicocca. Monza (MI), Italy

Background In pancreatic cancer patients, soluble factors produced by the tumor environment are often distributed to the circulatory system where they effect a generalized immunosuppression, resulting in reduced number and activity of T-lymphocytes subpopulations.

Aim To assess the effect of recombinant interleukin-2 (r-IL2), a cytokine with T-cell stimulating activity, on T-lymphocytes in pancreatic cancer patients.

Methods Twelve patients with resectable pancreatic adenocarcinoma received subcutaneous administration of r-IL-2 at high dose (12 millions IU/day) for 3 consecutive days prior to surgical radical resection (10 pancreaticoduodenectomies, one splenopancreatectomy, and one total pancreatectomy). We estimated the level of total T lymphocytes (CD3⁺) and their subsets (CD4⁺; CD8⁺; CD3⁺/CD16⁺CD56⁺) in peripheral blood before starting r-IL2 immunotherapy and on 1^st and 7^th postoperative days.

Results After preoperative rIL-2 administration and radical surgery, we observed a significant increase of CD3⁺ T lymphocytes, CD4⁺ helper and CD8⁺ cytotoxic T cells both on 1^st and 7^th postoperative days (P<0.05, comparing to baseline data), while CD3⁺/CD16⁺CD56⁺ T lymphocytes reached a significant enhancement only on 7^th day (P<0.002).

Conclusions The preoperative immunotherapy with high dose r-IL2 has been able to overcome the anergic state typical of pancreatic cancer patients, by expanding T-lymphocytes subpopulations. The high levels of T-cells obtained in these patients may strengthen their immune anticancer defense, reducing the dissemination of tumor cells in the peri-operative period.

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