PMID- 10702820
OWN - NLM
STAT- MEDLINE
DCOM- 20000816
LR  - 20051117
IS  - 0390-6078 (Print)
IS  - 0390-6078 (Linking)
VI  - 85
IP  - 3
DP  - 2000 Mar
TI  - Eosinophils and C4 predict clinical failure of combination immunotherapy with 
      very low dose subcutaneous interleukin-2 and interferon in renal cell carcinoma 
      patients.
PG  - 298-303
AB  - BACKGROUND AND 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. DESIGN AND 
      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. INTERPRETATION AND 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.
FAU - Moroni, M
AU  - Moroni M
AD  - Falck Division of Oncology, Niguarda-Ca' Granda Hospital, Milan, Italy.
FAU - Porta, C
AU  - Porta C
FAU - De Amici, M
AU  - De Amici M
FAU - Quaglini, S
AU  - Quaglini S
FAU - Cattabiani, M A
AU  - Cattabiani MA
FAU - Buzio, C
AU  - Buzio C
LA  - eng
PT  - Journal Article
PL  - Italy
TA  - Haematologica
JT  - Haematologica
JID - 0417435
RN  - 0 (Complement C4)
RN  - 0 (Interleukin-2)
RN  - 0 (Receptors, Interleukin-2)
RN  - 9008-11-1 (Interferons)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Carcinoma, Renal Cell/diagnosis/*drug therapy
MH  - Complement C4/*metabolism
MH  - Eosinophils/*cytology
MH  - Female
MH  - Humans
MH  - Immunotherapy
MH  - Injections, Subcutaneous
MH  - Interferons/*administration & dosage/blood
MH  - Interleukin-2/*administration & dosage/blood
MH  - Kidney Neoplasms/diagnosis/*drug therapy
MH  - Logistic Models
MH  - Lymphocytes/cytology
MH  - Male
MH  - Middle Aged
MH  - Prognosis
MH  - Receptors, Interleukin-2/blood
MH  - Solubility
MH  - T-Lymphocyte Subsets/cytology
MH  - Treatment Outcome
EDAT- 2000/03/07 09:00
MHDA- 2000/08/19 11:00
CRDT- 2000/03/07 09:00
PHST- 2000/03/07 09:00 [pubmed]
PHST- 2000/08/19 11:00 [medline]
PHST- 2000/03/07 09:00 [entrez]
PST - ppublish
SO  - Haematologica. 2000 Mar;85(3):298-303.