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Immunotherapy in surgical oncology.
420 HEUROE-INE P.Liseoni. Divisjon The recent enhanced knowledge of ca"cer immunobiology requires a revolution of both medical and surgical approaches in the treat nent of tumars,and the clinical investigation of cancer patientswould have to analyze not only the characteristics of neoplasms. but also the iwnunological status of patients. On the same way.ac cording to the imnobiologjcal knowledge. the surgical oncology would not to be limited to the removal of the -or mass.b~t also to the modification of host--r interactions in an attempt to improve host immune status by a bioswgical approach.T%is statement is justified by the fact that surgery-induced immunosuppression represents an unfavourable biological event.rhich could pr~o te the growth of nicrometastases responsible for recurrence in patients undergoing radjcal surgery. Tbhe fjrst purpose of the oer oocologlcal surgery consists of the possibility to remove tum-ar msss without further rorekng the i-na status of patients by a preoperative injection of antjtunor cytokines.nainly IL-2 bec.9~ se Of its essential role in generating the antitumor immune IYzaction. Major surgery has been proven to induce B decline in blood levels of IL-P.and this went would represent the dn q echmism responsible for surgery-induced jnnncaappression. m this b$ sis.severd studies of IL-2 preoperative administration have been performed in an attempt to investigate the possjbrlity ta succeesfully manipulate host immune performawe in the postoperative period.lt present. two main schedules have appeared to be able to completely abolish surgery-fnduced iwaunodeficiency in cancer patients,including declines in 1ymphocyte.T lympbocyte.NK cell and activated lymphocyte numbers.The fjrst schedule consists of IL-2 alone.given subcutaneously at 18 million Ill/day for 3 days before surgery.The second schedule,rhich 188 desjgned by taking into CT sideration the possibility to amplify IL-2 activity by imnomodulating neurohornanes,consjsts of low-dose s.C.IL-2(3 million Iuf day for 5 days)plus the pioeal hormone melat.,nin(40 &day orally).
WODULATION OF IL-2
ANTITUMOR ACTIWW.
S.Barni,A.~dizzoia.F.Peolorossi.G.Tanc~"*. of Oncological
Radiotherapy,San
Gerardo
Hospital
,Monza.
The recent advances In cancer psychonewoimunology have shorn that the in viva activities of cytokines are under a pbysjological newoendocrine regulatjon.unfortunately.despite it has been demonstrated that the newoendocrine status of cancer patients. mainly the circadian secretion of the pineal hormone nelatooin (MLT). may influence the clinic& effjcacy of cancer immunotherapies with cytokines.jncluding IL-2, the clinical applicatjon of cytokine biotberapies of cancer stjll continues to exclude the i! fluence of the neuroendocrine system on the antitumor irmnune response.Several "euroho-nes have appeared to play inwwnoregulatok-y effects,rith.hovever,very controversial resUlts.In contrast. ULT has been proven aleast constantly to exert an antitumar immw nostimulatory actioo.Advaoced cancer patients tend constantly to show an altered pineal functjon,mainly consisting of a reduced jl crease in MLT levels during the night. and experimental studjes have show that a pineal damage reduces the secretion and the activity of IL-P.The rationale of KLT and IL-2 association in the Immunotherapy of cancer is justified by the jmportance of the co? rection of at least one of the pineal deficiencies affecting cancer patients.In human studies have deranstrated the possibility to induce objective tumr regressions in advanced solid neoplasms refractory to IL-2 or progressing on IL-2 alone.ln a case-series of 250 ""treatable advanced solid t"mors,the "ewoinn"notherapy with low-dose subcutaneoue IL-2(3 million m/day in the evening for 6 days/week for d veeks)plus KLT(40 mg,day orally in the eveoing)has appeared to induce a tumor regression rate of 18% (parti cularly in hepatocarcinoma.gastrjc cmcer.cancer of pancreas,nonsmall cell lung cancer and endocrine tumors).rith a survival longer than 1 year in 43% paticnts,rbose life expectancy was less 6 months.Tberefore.at least for hepatocarcjnoma.cancer of pancreas.gastrjc cancer and lung aancer,at present the chenotherape_u tjc approach is not the only possible medical therapy of cancer, since at least in the name of the "par condicio" we have to consi der also the stratew of the neuroimmunotberapy as a oer ray.
WODULATION OF IL-2
ANTITUMOR ACTIWW.
S.Barni,A.~dizzoia.F.Peolorossi.G.Tanc~"*. of Oncological
Radiotherapy,San
Gerardo
Hospital
,Monza.
The recent advances In cancer psychonewoimunology have shorn that the in viva activities of cytokines are under a pbysjological newoendocrine regulatjon.unfortunately.despite it has been demonstrated that the newoendocrine status of cancer patients. mainly the circadian secretion of the pineal hormone nelatooin (MLT). may influence the clinic& effjcacy of cancer immunotherapies with cytokines.jncluding IL-2, the clinical applicatjon of cytokine biotberapies of cancer stjll continues to exclude the i! fluence of the neuroendocrine system on the antitumor irmnune response.Several "euroho-nes have appeared to play inwwnoregulatok-y effects,rith.hovever,very controversial resUlts.In contrast. ULT has been proven aleast constantly to exert an antitumar immw nostimulatory actioo.Advaoced cancer patients tend constantly to show an altered pineal functjon,mainly consisting of a reduced jl crease in MLT levels during the night. and experimental studjes have show that a pineal damage reduces the secretion and the activity of IL-P.The rationale of KLT and IL-2 association in the Immunotherapy of cancer is justified by the jmportance of the co? rection of at least one of the pineal deficiencies affecting cancer patients.In human studies have deranstrated the possibility to induce objective tumr regressions in advanced solid neoplasms refractory to IL-2 or progressing on IL-2 alone.ln a case-series of 250 ""treatable advanced solid t"mors,the "ewoinn"notherapy with low-dose subcutaneoue IL-2(3 million m/day in the evening for 6 days/week for d veeks)plus KLT(40 mg,day orally in the eveoing)has appeared to induce a tumor regression rate of 18% (parti cularly in hepatocarcinoma.gastrjc cmcer.cancer of pancreas,nonsmall cell lung cancer and endocrine tumors).rith a survival longer than 1 year in 43% paticnts,rbose life expectancy was less 6 months.Tberefore.at least for hepatocarcjnoma.cancer of pancreas.gastrjc cancer and lung aancer,at present the chenotherape_u tjc approach is not the only possible medical therapy of cancer, since at least in the name of the "par condicio" we have to consi der also the stratew of the neuroimmunotberapy as a oer ray.