title: Eosinophils and C4 predict clinical failure of combination immunotherapy with very low dose subcutaneous interleukin-2 and interferon in renal cell carcinoma patients.
abstract: OBJECTIVE
  The clinical and immunologic activities of interleukin-2 (IL-2) in cancer patients have been extensively studied and described; however, in most of these studies, IL-2 was administered by intravenous bolus or continuous infusion, while the immunologic effects of IL-2 given by the subcutaneous (s.c.) route have not yet been well studied.
  
  
  METHODS
  The present study was aimed at evaluating the effects of IL-2, given at very low doses s.c. to patients with advanced renal cell carcinoma (RCC), on a number of immunologic parameters: number of total lymphocytes, number of CD4-, CD8-, CD25-positive cells, number of natural killer (NK) cells, titers of IL-2 soluble receptor (sIL-2R) and of C4, eosinophils, eosinophilic cationic protein (ECP) and eosinophilic protein X (EPX). Finally, a logistic regression model was performed to identify early immunologic parameters that correlate with a favorable or unfavorable treatment outcome.
  
  
  RESULTS
  Independently from the mere report of the changes induced by immunotherapy, the analysis showed that, within the pre-treatment model, a large eosinophil number predicts the failure of IL-2 treatment; in contrast, within the post-treatment model, high C4 serum titers and, again, a large number of circulating eosinophils predict immunotherapy failure.
  
  
  CONCLUSIONS
  As far as concerns C4, its negative predictive value could be related to the fact that it is an indirect index of macrophage activation; thus, even though macrophages release substances with antitumor activity, they can also stimulate the release of sIL-2R, which may compete for exogenous IL-2. Some authors have postulated that macrophages may even stimulate tumor cell growth, or impair NK activity. Despite a great amount of uncertainty concerning the role of eosinophils, in our study, blood eosinophilia predicts a poor response to immunotherapy in patients with advanced RCC, thus supporting previous observations from our own group.
authors.affiliation: Falck Division of Oncology, Niguarda-Ca' Granda Hospital, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Moroni
authors.forename: C
authors.initials: C
authors.lastname: Porta
authors.forename: M
authors.initials: M
authors.lastname: De Amici
authors.forename: S
authors.initials: S
authors.lastname: Quaglini
authors.forename: M A
authors.initials: MA
authors.lastname: Cattabiani
authors.forename: C
authors.initials: C
authors.lastname: Buzio
mesh_terms: D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000188:drug therapy*; D003181:Complement C4 / Q000378:metabolism*; D004804:Eosinophils / Q000166:cytology*; D005260:Female; D006801:Humans; D007167:Immunotherapy; D007279:Injections, Subcutaneous; D007372:Interferons / Q000008:administration & dosage* / Q000097:blood; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000097:blood; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000188:drug therapy*; D016015:Logistic Models; D008214:Lymphocytes / Q000166:cytology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D015375:Receptors, Interleukin-2 / Q000097:blood; D012995:Solubility; D016176:T-Lymphocyte Subsets / Q000166:cytology; D016896:Treatment Outcome
chemical_list: D003181:Complement C4; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D007372:Interferons