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10.1245/s10434-006-9239-x
Annals of Surgical Oncology 14:1295-1304 (2007)
© 2007 Society of Surgical Oncology
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Original Article

Low-dose Interleukin-2 Administered Pre-operatively to Patients with Gastric Cancer Activates Peripheral and Peritumoral Lymphocytes But Does Not Affect Prognosis

Giovanni Carlo Cesana1, Fabrizio Romano1, Gaia Piacentini1, Marco Scotti1, Ambrogio Brenna2, Giorgio Bovo2, Massimo Vaghi3, Giacomo Aletti4, Roberto Caprotti1, Howard Kaufman5 and Franco Uggeri1

1 Department of General Surgery, University of Milano-Bicocca, S. Gerardo Hospital, via Donizzetti 106, Monza 20052, Milan, Italy
2 Department of Pathology, University of Milano-Bicocca, S. Gerardo Hospital, via Donizzetti 106, Monza 20052, Milan, Italy
3 Department of Clinical Oncology, University of Milano-Bicocca, S. Gerardo Hospital, via Donizzetti 106, Monza 20052 Milan, Italy
4 Department of Mathematics, University of Milan, Milan, Italy
5 Laboratory of Tumor Immunology, Department of Surgery, Columbia University, New York, NY, USA

Correspondence: Address correspondence and reprint requests to: Giovanni Carlo Cesana, E-mail: giovanni.cesana{at}gmail.com

Background: There is evidence that cancer is immunogenic under certain situations. IL-2 is described to stimulate an effective antitumor immune response in vitro and in vivo. The ability of cancer patients to undergo surgical resection is still the most important prognostic factor for many solid tumors, including gastric adenocarcinoma. The host immune system may be further compromised by surgical procedures leading to a generalized state of immunodepression in the post-operative period. The aim of this randomized case–control study is to evaluate the effects of pre-operative low-dose IL-2 treatment on patients with gastric adenocarcinoma who undergo surgery.

Methods: Sixty-eight patients with gastric adenocarcinoma were enrolled in the study and randomized in two groups: 36 patients were pre-treated with IL-2 and 32 underwent surgery without any treatment. Total peripheral WBC, neutrophils, CD3+ T, CD4+ T, CD8+ T and NK cells were obtained before and after surgery, at different times. Peritumoral infiltration was analyzed on all surgical specimens. Overall survival and relapse-free survival were studied with a median follow-up of 51 months.

Results: Low-dose IL-2 treatment resulted in an increase peritumoral lymphocytic and eosinophilic infiltrations and in a minor decrease in CD3+ T and CD4+ T cells after surgery (P < 0.05). A stepwise multivariate analysis revealed that overall survival and relapse-free survival were affected only by stage of tumor and age of patients.

Conclusions: According to our data low-doses of IL-2 administered pre-operatively to patients with gastric cancer activate peripheral and peri-tumoral lymphocytes but did not affect prognosis.

Key Words: Clinical trial • Gastric carcinoma • Interleukin-2 • Treatment






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