title: Preoperative IL-2 immunotherapy enhances tumor infiltrating lymphocytes (TILs) in gastric cancer patients.
abstract: OBJECTIVE
  Tumor infiltrating lymphocytes (TILs), recognized as a tumor-host reaction, have been linked to prognosis in various tumors, with a clear positive correlation between the density of the lymphoid infiltrate at the advancing margin of the tumor and the prognosis of the patients. TILs are somewhat activated by tumor associated antigens and by IL-2 endogenous release. The aim of this study is to verify if subcutaneously administered IL-2 is able to enhance TILs in gastric cancer patients and is able to influence the prognosis of the patients.
  
  
  METHODS
  We enrolled 39 consecutive patients with gastric adenocarcinoma. Patients were randomized to be treated with surgery alone (control group, 20 patients) or with surgery plus preoperative IL-2 (Interleukin-2) administration (treated group, 19 patients). Total lymphocytes, CD4 and CD4/CD8 were evaluated pre- and postoperatively. Peritumoral stromal reaction, neutrophils, lymphocytes and eosinophils infiltration in tumor histology were evaluated as well as survival curves and compared between the groups.
  
  
  RESULTS
  IL-2 treatment was safe and well tolerated, and in the IL-2 treated group a significant increase over the baseline pretreatment values of the total lymphocyte, CD4 and CD4/CD8 on both the 14th and 50th postoperative days was observed (p < 0.05). Peritumoral stromal reaction, neutrophils and eosinophils infiltration did not shown any statistical difference between the two groups. Otherwise we observed a statistically significant difference in the peri- and intratumoral lymphocytes infiltration between IL-2 treated and control patients (p = 0.000026). Median overall and disease-free survivals were longer, even if not significantly, in the IL-2 group than in the control arm (p = 0.089 and p = 0.09 respectively).
  
  
  CONCLUSIONS
  Our data shows that IL-2 seems to be able to induce substantial changes in the inflammatory infiltration of the neoplasm, improving the host activity toward the tumor and enhancing the TILs phenomenon in gastric cancer patients. This feature seems to improve the prognosis of the patients.
authors.affiliation: Department of General Surgery (Chirurgia I), San Gerardo Hospital II University of Milan-Bicocca, Monza, Italy. fabriziorom@hotmail.com
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Romano
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cesana
authors.forename: Roberto
authors.initials: R
authors.lastname: Caprotti
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bovo
authors.forename: Fabio
authors.initials: F
authors.lastname: Uggeri
authors.forename: Maria Gaia
authors.initials: MG
authors.lastname: Piacentini
authors.forename: Stefano
authors.initials: S
authors.lastname: Crippa
authors.forename: Franco
authors.initials: F
authors.lastname: Uggeri
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000601:surgery / Q000628:therapy*; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D005260:Female; D005743:Gastrectomy; D006801:Humans; D007167:Immunotherapy; D007376:Interleukin-2 / Q000008:administration & dosage*; D018655:Lymphocyte Count; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011300:Preoperative Care; D013274:Stomach Neoplasms / Q000276:immunology / Q000601:surgery / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007376:Interleukin-2