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Published in: Annals of Surgical Oncology 4/2007

01-04-2007 | Gastrointestinal Oncology

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

Authors: Giovanni Carlo Cesana, Fabrizio Romano, Gaia Piacentini, Marco Scotti, Ambrogio Brenna, Giorgio Bovo, Massimo Vaghi, Giacomo Aletti, Roberto Caprotti, Howard Kaufman, Franco Uggeri

Published in: Annals of Surgical Oncology | Issue 4/2007

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Abstract

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.
Literature
1.
go back to reference Parkin DM, Bray FI, Devesa SS. Cancer burden in the year 2000. The global picture. Eur J Cancer 2001; 37(Suppl 8):S4–66CrossRef Parkin DM, Bray FI, Devesa SS. Cancer burden in the year 2000. The global picture. Eur J Cancer 2001; 37(Suppl 8):S4–66CrossRef
2.
go back to reference Crew KD, Neugut AI. Epidemiology of gastric cancer. World J Gastroenterol 2006; 12(3):354–62PubMed Crew KD, Neugut AI. Epidemiology of gastric cancer. World J Gastroenterol 2006; 12(3):354–62PubMed
3.
go back to reference Devesa SS, Blot WJ, Fraumeni JF. Changing patterns in the incidence of esophageal and gastric carcinoma in the United States. Cancer 1998; 83:2049–53PubMedCrossRef Devesa SS, Blot WJ, Fraumeni JF. Changing patterns in the incidence of esophageal and gastric carcinoma in the United States. Cancer 1998; 83:2049–53PubMedCrossRef
4.
go back to reference Powell J, McConkey CC. Increasing incidence of adenocarcinoma of the gastric cardia and adjacent sites. Br J Cancer 1990; 62:440–3PubMed Powell J, McConkey CC. Increasing incidence of adenocarcinoma of the gastric cardia and adjacent sites. Br J Cancer 1990; 62:440–3PubMed
5.
go back to reference Laheij RJ, Straatman H, Verbeek AL, et al. Mortality trend from cancer of the gastric cardia in The Netherlands, 1969–1994. Int J Epidemiol 1999; 28:391–5PubMedCrossRef Laheij RJ, Straatman H, Verbeek AL, et al. Mortality trend from cancer of the gastric cardia in The Netherlands, 1969–1994. Int J Epidemiol 1999; 28:391–5PubMedCrossRef
6.
go back to reference Botterweck AA, Schouten LJ, Volovics A, et al. Trends in incidence of adenocarcinoma of the oesophagus and gastric cardia in ten European countries. Int J Epidemiol 2000; 29:645–54PubMedCrossRef Botterweck AA, Schouten LJ, Volovics A, et al. Trends in incidence of adenocarcinoma of the oesophagus and gastric cardia in ten European countries. Int J Epidemiol 2000; 29:645–54PubMedCrossRef
7.
go back to reference GLOBOCAN 2000: Cancer incidence, mortality and prevalence worldwide. International Agency for Research on Cancer (IARC), Lyon: IARC Press; 2001 GLOBOCAN 2000: Cancer incidence, mortality and prevalence worldwide. International Agency for Research on Cancer (IARC), Lyon: IARC Press; 2001
8.
go back to reference Hundahl SA, Phillips JL, Menck HR. The National Cancer Data Base report on survival of U.S. gastric carcinoma patients treated with gastrectomy. Cancer 2000; 88:912–32CrossRef Hundahl SA, Phillips JL, Menck HR. The National Cancer Data Base report on survival of U.S. gastric carcinoma patients treated with gastrectomy. Cancer 2000; 88:912–32CrossRef
9.
go back to reference Lennard TW, Shenton BK, Borzotta A, et al. The influence of surgical operations on components of the human immune system. Br J Surg 1985; 72(10):771–6PubMedCrossRef Lennard TW, Shenton BK, Borzotta A, et al. The influence of surgical operations on components of the human immune system. Br J Surg 1985; 72(10):771–6PubMedCrossRef
10.
go back to reference Wakefield CH, Carey PD, Foulds S, et al. Changes in major histocompatibility complex class II expression in monocytes and T cells of patients developing infection after surgery. Br J Surg 1993; 80:205–9PubMedCrossRef Wakefield CH, Carey PD, Foulds S, et al. Changes in major histocompatibility complex class II expression in monocytes and T cells of patients developing infection after surgery. Br J Surg 1993; 80:205–9PubMedCrossRef
11.
go back to reference Cheadle WG, Hershman MJ, Wellhausen SR, et al. HLA-DR antigen expression on peripheral blood monocytes correlates with surgical infection. Am J Surg 1991; 161:639–45PubMedCrossRef Cheadle WG, Hershman MJ, Wellhausen SR, et al. HLA-DR antigen expression on peripheral blood monocytes correlates with surgical infection. Am J Surg 1991; 161:639–45PubMedCrossRef
12.
go back to reference Eggermont AMM, Steller EP, Sugerbacker PH. Laparotomy enhances intraperitoneal tumour growth and abrogates the antitumor effects of interleukin-2 and lymphokine-activated killer cells. Surgery 1987; 102:71–8PubMed Eggermont AMM, Steller EP, Sugerbacker PH. Laparotomy enhances intraperitoneal tumour growth and abrogates the antitumor effects of interleukin-2 and lymphokine-activated killer cells. Surgery 1987; 102:71–8PubMed
13.
go back to reference Morgan D, Ruscetti F, Gallo R. Selective in vitro growth of T lymphocytes from normal human bone marrows. Science 1976; 193:1007–8PubMedCrossRef Morgan D, Ruscetti F, Gallo R. Selective in vitro growth of T lymphocytes from normal human bone marrows. Science 1976; 193:1007–8PubMedCrossRef
14.
go back to reference Smith KA. Interleukin-2: inception, impact and implications. Science 1998; 240:1169–76CrossRef Smith KA. Interleukin-2: inception, impact and implications. Science 1998; 240:1169–76CrossRef
15.
go back to reference Rosenberg SA, Lotze MT, Muul LM, et al. A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high dose interleukin-2 alone. N Engl J Med 1997; 316:889–97CrossRef Rosenberg SA, Lotze MT, Muul LM, et al. A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high dose interleukin-2 alone. N Engl J Med 1997; 316:889–97CrossRef
16.
go back to reference Kovacs JA, Baseler M, Dewar RJ, et al. Increases in CD4 T lymphocytes with intermittent courses of interleukin-2 in patients with human immunodeficiency virus infection. A preliminary study. N Engl J Med 1995; 332(9):567–75PubMedCrossRef Kovacs JA, Baseler M, Dewar RJ, et al. Increases in CD4 T lymphocytes with intermittent courses of interleukin-2 in patients with human immunodeficiency virus infection. A preliminary study. N Engl J Med 1995; 332(9):567–75PubMedCrossRef
17.
go back to reference Levy Y, Capitant C, Houhou S, et al. Comparison of subcutaneous and intravenous interleukin-2 in asymptomatic HIV-1 infection: a randomised controlled trial. ANRS 048 study group. Lancet 1999; 353(9168):1923–9PubMedCrossRef Levy Y, Capitant C, Houhou S, et al. Comparison of subcutaneous and intravenous interleukin-2 in asymptomatic HIV-1 infection: a randomised controlled trial. ANRS 048 study group. Lancet 1999; 353(9168):1923–9PubMedCrossRef
18.
go back to reference Jacobson EL, Pilaro F, Smith KA. Rational interleukin 2 therapy for HIV positive individuals: daily low doses enhance immune function without toxicity. Proc Natl Acad Sci USA 1996; 93(19):10405–10PubMedCrossRef Jacobson EL, Pilaro F, Smith KA. Rational interleukin 2 therapy for HIV positive individuals: daily low doses enhance immune function without toxicity. Proc Natl Acad Sci USA 1996; 93(19):10405–10PubMedCrossRef
19.
go back to reference Grande C, Firvida JL, Navas V, et al. Interleukin-2 for the treatment of solid tumors other than melanoma and renal cell carcinoma. Anticancer Drugs 2006; 17(1):1–12PubMedCrossRef Grande C, Firvida JL, Navas V, et al. Interleukin-2 for the treatment of solid tumors other than melanoma and renal cell carcinoma. Anticancer Drugs 2006; 17(1):1–12PubMedCrossRef
20.
go back to reference Repka T, Cbiorean EG, Gay J, et al. Trastuzumab and IL-2 in HER-2 positive metastatic breast cancer: a pilot study. Clin Cancer Res 2003; 9:2440–6PubMed Repka T, Cbiorean EG, Gay J, et al. Trastuzumab and IL-2 in HER-2 positive metastatic breast cancer: a pilot study. Clin Cancer Res 2003; 9:2440–6PubMed
21.
go back to reference Fleming GF, Meropol NJ, Rosner GL, et al. A phase I trial of escalating doses of trastuzumab combined with daily subcutaneous interleukin-2: report of cancer and leukaemia group B 9661. Clin Cancer Res 2002; 8:3718–27PubMed Fleming GF, Meropol NJ, Rosner GL, et al. A phase I trial of escalating doses of trastuzumab combined with daily subcutaneous interleukin-2: report of cancer and leukaemia group B 9661. Clin Cancer Res 2002; 8:3718–27PubMed
22.
go back to reference Dagher R, Long LM, Read EJ, et al. Pilot trial of tumor specific peptide vaccination and continuous infusion interleukin-2 in patients with recurrent Ewing sarcoma and alveolar rhabdomyosarcoma: an inter-institute NIH study. Med Pediatr Oncol 2002; 38:158–64PubMedCrossRef Dagher R, Long LM, Read EJ, et al. Pilot trial of tumor specific peptide vaccination and continuous infusion interleukin-2 in patients with recurrent Ewing sarcoma and alveolar rhabdomyosarcoma: an inter-institute NIH study. Med Pediatr Oncol 2002; 38:158–64PubMedCrossRef
23.
go back to reference Fiedler W, Kruger W, Laack E, et al. A clinical trial of edrecolomab, interleukin-2 and GM-CSF in patients with advanced colorectal cancer. Oncol Rep 2001; 8:225–31PubMed Fiedler W, Kruger W, Laack E, et al. A clinical trial of edrecolomab, interleukin-2 and GM-CSF in patients with advanced colorectal cancer. Oncol Rep 2001; 8:225–31PubMed
24.
go back to reference Sosman JA, Stiff P, Moss SM, et al. Pilot trial of interleukin-2 with granulocyte colony stimulating factor for the mobilization of progenitor cells in advanced breast cancer patients undergoing high-dose chemotherapy. J Clin Oncol 2001; 19:634–44PubMed Sosman JA, Stiff P, Moss SM, et al. Pilot trial of interleukin-2 with granulocyte colony stimulating factor for the mobilization of progenitor cells in advanced breast cancer patients undergoing high-dose chemotherapy. J Clin Oncol 2001; 19:634–44PubMed
25.
go back to reference Freedman RS, Kudelka AP, Kavanagh JJ, et al. Clinical and biological effects of intraperitoneal interferon gamma and recombinant interleukin with or without tumor infiltrating lymphocytes in patients with ovarian or peritoneal carcinoma. Clin Cancer Res 2000; 6:2268–78PubMed Freedman RS, Kudelka AP, Kavanagh JJ, et al. Clinical and biological effects of intraperitoneal interferon gamma and recombinant interleukin with or without tumor infiltrating lymphocytes in patients with ovarian or peritoneal carcinoma. Clin Cancer Res 2000; 6:2268–78PubMed
26.
go back to reference Tester WJ, Kim KM, Krigel RL, et al. A randomized phase II study of interleukin-2 with or without beta-interferon for patients with advanced non-small cell lung cancer. A Eastern Cooperative Oncology Group study (PZ586). Lung Cancer 1999; 25:199–206PubMedCrossRef Tester WJ, Kim KM, Krigel RL, et al. A randomized phase II study of interleukin-2 with or without beta-interferon for patients with advanced non-small cell lung cancer. A Eastern Cooperative Oncology Group study (PZ586). Lung Cancer 1999; 25:199–206PubMedCrossRef
27.
go back to reference Meehan KR, Arun B, Gehan EA, et al. Immunotherapy with interleukin-2 and alpha interferon after interleukin-2 activated hematopoietic stem cell transplantation for breast cancer. Bone Marrow Transplant 1999; 23:667–73PubMedCrossRef Meehan KR, Arun B, Gehan EA, et al. Immunotherapy with interleukin-2 and alpha interferon after interleukin-2 activated hematopoietic stem cell transplantation for breast cancer. Bone Marrow Transplant 1999; 23:667–73PubMedCrossRef
28.
go back to reference Luksch R, Perotti D, Cefalo G, et al. Immunomodulation in a treatment program including pre- and post- operative interleukin-2 and chemotherapy for childhood osteosarcoma. Tumori 2003; 89:263–8PubMed Luksch R, Perotti D, Cefalo G, et al. Immunomodulation in a treatment program including pre- and post- operative interleukin-2 and chemotherapy for childhood osteosarcoma. Tumori 2003; 89:263–8PubMed
29.
go back to reference Mantovani G, Maccio A, Mulas C, et al. Dose-intense phase II study of weekly cisplatin and epidoxorubicin plus medroxyprogesterone acetate and recombinant interleukin-2 in stage IIIB-IV non-small cell lung cancer. Oncol Rep 2002; 9:661–70PubMed Mantovani G, Maccio A, Mulas C, et al. Dose-intense phase II study of weekly cisplatin and epidoxorubicin plus medroxyprogesterone acetate and recombinant interleukin-2 in stage IIIB-IV non-small cell lung cancer. Oncol Rep 2002; 9:661–70PubMed
30.
go back to reference Yoshimura K, Hazama S, Iizuka N, et al. Hepatic arterial infusion of IL-2 and chemotherapy for unresectable liver metastases from colorectal cancer. Gan To Kagaku Ryoho 2002; 29:2117–20PubMed Yoshimura K, Hazama S, Iizuka N, et al. Hepatic arterial infusion of IL-2 and chemotherapy for unresectable liver metastases from colorectal cancer. Gan To Kagaku Ryoho 2002; 29:2117–20PubMed
31.
go back to reference Fu QG, Meng FD, Shen XD, et al. Efficacy of intraperitoneal thermochemotherapy and immunotherapy in intraperitoneal recurrence after gastrointestinal cancer resection. World J Gastroenterol 2002; 8:1019–22PubMed Fu QG, Meng FD, Shen XD, et al. Efficacy of intraperitoneal thermochemotherapy and immunotherapy in intraperitoneal recurrence after gastrointestinal cancer resection. World J Gastroenterol 2002; 8:1019–22PubMed
32.
go back to reference Toh HC, McAfee SL, Sackstein R, et al. High-dose cyclophosphamide+carboplatin and interleukin-2 activated autologous stem cell transplantation followed by maintenance interleukin-2 therapy in metastatic breast carcinoma. A phase II study. Bone Marrow Transplant 2000; 25:19–24PubMedCrossRef Toh HC, McAfee SL, Sackstein R, et al. High-dose cyclophosphamide+carboplatin and interleukin-2 activated autologous stem cell transplantation followed by maintenance interleukin-2 therapy in metastatic breast carcinoma. A phase II study. Bone Marrow Transplant 2000; 25:19–24PubMedCrossRef
33.
go back to reference Le Cesne A, Vassal G, Farace F, et al. Combination interleukin-2 and doxorubicin in advanced adult solid tumors: circumvention of doxorubicin resistance in soft tissue sarcoma? J Immunother 1999; 22:268–77PubMedCrossRef Le Cesne A, Vassal G, Farace F, et al. Combination interleukin-2 and doxorubicin in advanced adult solid tumors: circumvention of doxorubicin resistance in soft tissue sarcoma? J Immunother 1999; 22:268–77PubMedCrossRef
34.
go back to reference Angelini C, Bovo G, Muselli P, et al. Preoperative interleukin-2 immunotherapy in pancreatic cancer: preliminary results. Hepatogastroenterology 2006; 53(67):141–4PubMed Angelini C, Bovo G, Muselli P, et al. Preoperative interleukin-2 immunotherapy in pancreatic cancer: preliminary results. Hepatogastroenterology 2006; 53(67):141–4PubMed
35.
go back to reference Romano F, Cesana G, Berselli M, et al. Biological, histological, and clinical impact of preoperative IL-2 administration in radically operable gastric cancer patients. J Surg Oncol 2004; 88(4):240–7PubMedCrossRef Romano F, Cesana G, Berselli M, et al. Biological, histological, and clinical impact of preoperative IL-2 administration in radically operable gastric cancer patients. J Surg Oncol 2004; 88(4):240–7PubMedCrossRef
36.
go back to reference Kishiwada M, Kawarada Y, Taoka H, et al. Management of advanced pancreatic cancer: staging laparoscopy and immunochemotherapy. A new treatment strategy. Hepatogastroenterology 2002; 49:1704–6PubMed Kishiwada M, Kawarada Y, Taoka H, et al. Management of advanced pancreatic cancer: staging laparoscopy and immunochemotherapy. A new treatment strategy. Hepatogastroenterology 2002; 49:1704–6PubMed
37.
go back to reference Yano T, Sugio K, Yamazaki K, et al. Postoperative adjuvant adoptive immunotherapy with lymph node-LAK cells and IL-2 for pathologic stage I non-small cell lung cancer. Lung Cancer 1999; 26:143–8PubMedCrossRef Yano T, Sugio K, Yamazaki K, et al. Postoperative adjuvant adoptive immunotherapy with lymph node-LAK cells and IL-2 for pathologic stage I non-small cell lung cancer. Lung Cancer 1999; 26:143–8PubMedCrossRef
38.
go back to reference Tarasov VA, Filatov MV, Kisliakova TV, et al. Combined surgical and immunotherapeutic treatment of patients with fourth stage colon cancer. Hybridoma 1999; 18:99–102PubMedCrossRef Tarasov VA, Filatov MV, Kisliakova TV, et al. Combined surgical and immunotherapeutic treatment of patients with fourth stage colon cancer. Hybridoma 1999; 18:99–102PubMedCrossRef
39.
go back to reference Lygidakis NJ, Berberabe AE, Spentzouris N, et al. A prospective randomized study using adjuvant locoregional chemoimmunotherapy in combination with surgery for pancreatic carcinoma. Hepatogastroenterology 1999; 45:2376–81 Lygidakis NJ, Berberabe AE, Spentzouris N, et al. A prospective randomized study using adjuvant locoregional chemoimmunotherapy in combination with surgery for pancreatic carcinoma. Hepatogastroenterology 1999; 45:2376–81
40.
go back to reference Melioli G, Ratto GB, Ponte M, et al. Treatment of stage IIIB non-small-cell lung cancer with surgery followed by infusion of tumor infiltrating lymphocytes and recombinant interleukin-2: a pilot study. J Immunother 1996; 19:224–30CrossRef Melioli G, Ratto GB, Ponte M, et al. Treatment of stage IIIB non-small-cell lung cancer with surgery followed by infusion of tumor infiltrating lymphocytes and recombinant interleukin-2: a pilot study. J Immunother 1996; 19:224–30CrossRef
41.
go back to reference Wang Y, Gu Q, Liu B, et al. Perspectives of SEREX-defined antigens in diagnosis and immunotherapy for gastric cancer. Cancer Biol Ther 2004; 3(9):806–11PubMedCrossRef Wang Y, Gu Q, Liu B, et al. Perspectives of SEREX-defined antigens in diagnosis and immunotherapy for gastric cancer. Cancer Biol Ther 2004; 3(9):806–11PubMedCrossRef
42.
go back to reference Lissoni P, Brivio F, Ardizzoia A, et al. Subcutaneous therapy with low-dose interleukin-2 plus the neurohormone melatonin in metastatic gastric cancer patients with low performance status. Clin Tumori 1993; 79(6):401–4 Lissoni P, Brivio F, Ardizzoia A, et al. Subcutaneous therapy with low-dose interleukin-2 plus the neurohormone melatonin in metastatic gastric cancer patients with low performance status. Clin Tumori 1993; 79(6):401–4
43.
go back to reference Lissoni P, Barni S, Ardizzoia A, et al. Cancer immunotherapy with low-dose interleukin-2 subcutaneous administration: potential efficacy in most solid tumor histotypes by a concomitant treatment with the pineal hormone melatonin. J Biol Regul Homeost Agents 1993; 7(4):121–5PubMed Lissoni P, Barni S, Ardizzoia A, et al. Cancer immunotherapy with low-dose interleukin-2 subcutaneous administration: potential efficacy in most solid tumor histotypes by a concomitant treatment with the pineal hormone melatonin. J Biol Regul Homeost Agents 1993; 7(4):121–5PubMed
44.
go back to reference Gochi A, Orita K, Fuchimoto S, et al. The prognostic advantage of preoperative intratumoral injection of OK-432 for gastric cancer patients. Br J Cancer 2001; 84(4):443–451PubMedCrossRef Gochi A, Orita K, Fuchimoto S, et al. The prognostic advantage of preoperative intratumoral injection of OK-432 for gastric cancer patients. Br J Cancer 2001; 84(4):443–451PubMedCrossRef
45.
go back to reference Sakamoto J, Teramukai S, Nakazato H, et al. Efficacy of adjuvant immunochemotherapy with OK-432 for patients with curatively resected gastric cancer: a meta-analysis of centrally randomized controlled clinical trials. J Immunother 2002; 25(5):405–12PubMedCrossRef Sakamoto J, Teramukai S, Nakazato H, et al. Efficacy of adjuvant immunochemotherapy with OK-432 for patients with curatively resected gastric cancer: a meta-analysis of centrally randomized controlled clinical trials. J Immunother 2002; 25(5):405–12PubMedCrossRef
46.
go back to reference Brivio F, Fumagalli L, Lissoni P, et al. Pre-operative immunoprophylaxis with interleukin-2 may improve prognosis in radical surgery for colorectal cancer stage B–C. Anticancer Res 2006; 26(1B):599–603PubMed Brivio F, Fumagalli L, Lissoni P, et al. Pre-operative immunoprophylaxis with interleukin-2 may improve prognosis in radical surgery for colorectal cancer stage B–C. Anticancer Res 2006; 26(1B):599–603PubMed
47.
go back to reference Brivio F, Lissoni P, Gilardi R, et al. Abrogation of surgery-induced decline in circulating dentritic cells by subcutaneous preoperative administration of IL-2 in operable cancer patients. J Biol Regul Homeost Agents 2000; 14(3):200–3PubMed Brivio F, Lissoni P, Gilardi R, et al. Abrogation of surgery-induced decline in circulating dentritic cells by subcutaneous preoperative administration of IL-2 in operable cancer patients. J Biol Regul Homeost Agents 2000; 14(3):200–3PubMed
48.
go back to reference Brivio F, Lissoni P, Alderi G, et al. Preoperative interleukin-2 subcutaneous immunotherapy may prolong the survival time in advanced colorectal cancer patients. Oncology 1996; 53:263–8PubMedCrossRef Brivio F, Lissoni P, Alderi G, et al. Preoperative interleukin-2 subcutaneous immunotherapy may prolong the survival time in advanced colorectal cancer patients. Oncology 1996; 53:263–8PubMedCrossRef
49.
go back to reference Ropponen KM, Eskilinen MJ, Lipponen PK, et al. Prognostic value of tumor infiltrating lymphocytes (TILs) in colorectal cancer. J Pathol 1997; 182:318–24PubMedCrossRef Ropponen KM, Eskilinen MJ, Lipponen PK, et al. Prognostic value of tumor infiltrating lymphocytes (TILs) in colorectal cancer. J Pathol 1997; 182:318–24PubMedCrossRef
50.
go back to reference Cerea K, Romano F, Bravo AF, et al. Phase IB study on prevention of surgery-induced immunodeficiency with preoperative administration of low-dose subcutaneous interleukin-2 in gastric cancer patients. J Surg Oncol 2001; 78(1):32–7PubMedCrossRef Cerea K, Romano F, Bravo AF, et al. Phase IB study on prevention of surgery-induced immunodeficiency with preoperative administration of low-dose subcutaneous interleukin-2 in gastric cancer patients. J Surg Oncol 2001; 78(1):32–7PubMedCrossRef
51.
52.
53.
go back to reference Atkins MB, Lotze MT, Dutcher JP, et al. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol 1999; 17(7):2105–16PubMed Atkins MB, Lotze MT, Dutcher JP, et al. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol 1999; 17(7):2105–16PubMed
54.
go back to reference Fyfe G, Fisher RI, Rosenberg SA, et al. Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy. J Clin Oncol 1995; 13:688–96PubMed Fyfe G, Fisher RI, Rosenberg SA, et al. Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy. J Clin Oncol 1995; 13:688–96PubMed
55.
go back to reference Fisher RI, Coltman CA Jr, Doroshow JH, et al. Metastatic renal cancer treated with interleukin-2 and lymphokine-activated killer cells. A phase II clinical trial. Ann Intern Med 1988; 108(4):518–23PubMed Fisher RI, Coltman CA Jr, Doroshow JH, et al. Metastatic renal cancer treated with interleukin-2 and lymphokine-activated killer cells. A phase II clinical trial. Ann Intern Med 1988; 108(4):518–23PubMed
56.
go back to reference Rosenberg SA, Yang JC, White DE, et al. Durability of complete responses in patients with metastatic cancer treated with high-dose interleukin-2. Ann Surg 1998; 228:319CrossRef Rosenberg SA, Yang JC, White DE, et al. Durability of complete responses in patients with metastatic cancer treated with high-dose interleukin-2. Ann Surg 1998; 228:319CrossRef
57.
go back to reference Fisher RI, Rosenberg SA, Sznol M, et al. High-dose aldesleukin in renal cell carcinoma: long term survival update. Cancer J Sci Am 1997; 3:S70–2PubMed Fisher RI, Rosenberg SA, Sznol M, et al. High-dose aldesleukin in renal cell carcinoma: long term survival update. Cancer J Sci Am 1997; 3:S70–2PubMed
58.
go back to reference Cesana GC, DeRaffele G, Cohen S, et al. Characterization of CD4+CD25+ regulatory T cells in patients treated with high-dose interleukin-2 for metastatic melanoma or renal cell carcinoma. J Clin Oncol 2006; 24:1169–77PubMedCrossRef Cesana GC, DeRaffele G, Cohen S, et al. Characterization of CD4+CD25+ regulatory T cells in patients treated with high-dose interleukin-2 for metastatic melanoma or renal cell carcinoma. J Clin Oncol 2006; 24:1169–77PubMedCrossRef
59.
go back to reference Kodera Y, Fujiwara M, Koike M, et al. Chemotherapy as a component of multimodal therapy for gastric carcinoma. World J Gastroenterol 2006; 12(13):2000–5PubMed Kodera Y, Fujiwara M, Koike M, et al. Chemotherapy as a component of multimodal therapy for gastric carcinoma. World J Gastroenterol 2006; 12(13):2000–5PubMed
60.
go back to reference Wang E, Panelli MC, Monsurro V, et al. A global approach to tumor immunology. Cell Mol Immunol 2004; 1(4):256–65PubMed Wang E, Panelli MC, Monsurro V, et al. A global approach to tumor immunology. Cell Mol Immunol 2004; 1(4):256–65PubMed
61.
go back to reference Bovo G, Brivio F, Brenna A, et al. Pre-operative interleukin-2 immunotherapy induces eosinophilic infiltration in colorectal neoplastic stroma. Pathologica 1995; 87(2):135–8PubMed Bovo G, Brivio F, Brenna A, et al. Pre-operative interleukin-2 immunotherapy induces eosinophilic infiltration in colorectal neoplastic stroma. Pathologica 1995; 87(2):135–8PubMed
62.
go back to reference Silberstein DS, Schoof DD, Rodrick ML, et al. Activation of eosinophils in cancer patients treated with IL-2 and IL-2-generated lymphokine-activated killer cells. J Immunol 1989; 142(6):2162–7PubMed Silberstein DS, Schoof DD, Rodrick ML, et al. Activation of eosinophils in cancer patients treated with IL-2 and IL-2-generated lymphokine-activated killer cells. J Immunol 1989; 142(6):2162–7PubMed
63.
go back to reference Villegas FR, Coca S, Villarrubia VG, et al. Prognostic significance of tumor infiltrating natural killer cells subset CD57 in patients with squamous cell lung cancer. Lung Cancer 2002; 35:23–8PubMedCrossRef Villegas FR, Coca S, Villarrubia VG, et al. Prognostic significance of tumor infiltrating natural killer cells subset CD57 in patients with squamous cell lung cancer. Lung Cancer 2002; 35:23–8PubMedCrossRef
64.
go back to reference Friedl J, Stift A, Paolini P, et al. Tumor antigen pulsed dendritic cells enhance the cytolityc activity of tumor-infiltrating lymphocytes in human hepatocellular cancer. Cancer Biother Radiopharm 2000; 15:477–86PubMedCrossRef Friedl J, Stift A, Paolini P, et al. Tumor antigen pulsed dendritic cells enhance the cytolityc activity of tumor-infiltrating lymphocytes in human hepatocellular cancer. Cancer Biother Radiopharm 2000; 15:477–86PubMedCrossRef
65.
go back to reference Zhang L, Conejo-Garcia JR, Katsaros D, et al. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med 2003; 348(3):203–13PubMedCrossRef Zhang L, Conejo-Garcia JR, Katsaros D, et al. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med 2003; 348(3):203–13PubMedCrossRef
66.
go back to reference Coca S, Perez-Piqueras J, Martinez D, et al. The prognostic significance of intratumoral natural killer cells in patients with colorectal carcinoma. Cancer 1997; 79:2320–8PubMedCrossRef Coca S, Perez-Piqueras J, Martinez D, et al. The prognostic significance of intratumoral natural killer cells in patients with colorectal carcinoma. Cancer 1997; 79:2320–8PubMedCrossRef
67.
go back to reference Pagès F, Berger A, Camus M, et al. Effector memory T cells, early metastasis, and survival in colorectal cancer. N Engl J Med 2005; 353:2654–66PubMedCrossRef Pagès F, Berger A, Camus M, et al. Effector memory T cells, early metastasis, and survival in colorectal cancer. N Engl J Med 2005; 353:2654–66PubMedCrossRef
68.
go back to reference Vesalainen S, Lipponen P, Taljia M, et al. Histological grade, perineural infiltration, tumor-infiltrating lymphocytes and apoptosis as determinants of long-term prognosis in prostatic adenocarcinoma. Eur J Cancer 1994; 30:1797–1803CrossRef Vesalainen S, Lipponen P, Taljia M, et al. Histological grade, perineural infiltration, tumor-infiltrating lymphocytes and apoptosis as determinants of long-term prognosis in prostatic adenocarcinoma. Eur J Cancer 1994; 30:1797–1803CrossRef
69.
go back to reference Setala LP, Kosma VM, Marin S, et al. Prognostic factors in gastric cancer: the value of vascular invasion, mitotic rate and lymphoplasmacytic infiltration. Br J Cancer 1996; 74:766–772PubMed Setala LP, Kosma VM, Marin S, et al. Prognostic factors in gastric cancer: the value of vascular invasion, mitotic rate and lymphoplasmacytic infiltration. Br J Cancer 1996; 74:766–772PubMed
70.
go back to reference Yang JC, Sherry RM, Steinberg SM, et al. Randomized study of high-dose and low-dose interleukin-2 in patients with metastatic renal cancer. J Clin Oncol 2003; 21(16):3127–32PubMedCrossRef Yang JC, Sherry RM, Steinberg SM, et al. Randomized study of high-dose and low-dose interleukin-2 in patients with metastatic renal cancer. J Clin Oncol 2003; 21(16):3127–32PubMedCrossRef
Metadata
Title
Low-dose Interleukin-2 Administered Pre-operatively to Patients with Gastric Cancer Activates Peripheral and Peritumoral Lymphocytes But Does Not Affect Prognosis
Authors
Giovanni Carlo Cesana
Fabrizio Romano
Gaia Piacentini
Marco Scotti
Ambrogio Brenna
Giorgio Bovo
Massimo Vaghi
Giacomo Aletti
Roberto Caprotti
Howard Kaufman
Franco Uggeri
Publication date
01-04-2007
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 4/2007
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-006-9239-x

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