Interleukin-2 immunotherapy action on innate immunity cells in peripheral blood and tumoral tissue of pancreatic adenocarcinoma patients.
OBJECTIVE
Innate immunity cells play a crucial role in host anticancer defense: cancer patients with high levels of natural killer (NK) cells and eosinophils have a better prognosis. Recombinant interleukin-2 (rIL-2) immunotherapy stimulates innate immunity cells. This study aims to evaluate the toxicity of pre- and postoperative rIL-2 treatment and the effects on innate immunity both in peripheral blood and in cancer tissue of patients with resectable pancreatic adenocarcinoma.


METHODS
Seventeen patients received high dose rIL-2 preoperative subcutaneous administration and two low dose postoperative cycles. We evaluated NK cell and eosinophil count in blood and in pancreatic surgical specimens.


RESULTS
Toxicity was moderate. In the early postoperative period, blood NK cells and eosinophils significantly increased compared to basal values (p < 0.02). Histopathological analysis did not find significant intratumoral infiltration of NK cells nor of eosinophils.


CONCLUSIONS
Preoperative high dose rIL-2 administration is able to counteract surgery-induced deficiency of NK cells and eosinophils in peripheral blood in the early postoperative period, although it cannot overcome local mechanisms of immune tumor escape in cancer tissue. The amplification of innate immunity, induced by immunotherapy, may improve the control of metastatic cells spreading in the perioperative period.
Degrate
Luca
L
Department of General Surgery, San Gerardo Hospital, University of Milano-Bicocca, via Pergolesi 33, 20052, Monza, Milan, Italy. degluc@inwind.it
Nobili
Cinzia
C
Franciosi
Claudio
C
Caprotti
Roberto
R
Brivio
Fernando
F
Romano
Fabrizio
F
Leone
Biagio Eugenio
BE
Trezzi
Rosangela
R
Uggeri
Franco
F
D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy* / Q000276:immunology* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects* / Q000276:immunology*; D007167:Immunotherapy / Q000379:methods*; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000601:surgery; D016577:Pancreaticoduodenectomy; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use
D000970:Antineoplastic Agents; D007376:Interleukin-2; D011994:Recombinant Proteins; C082598:aldesleukin