Eosinophils and C4 predict clinical failure of combination immunotherapy with very low dose subcutaneous interleukin-2 and interferon in renal cell carcinoma patients

Citation
M. Moroni et al., Eosinophils and C4 predict clinical failure of combination immunotherapy with very low dose subcutaneous interleukin-2 and interferon in renal cell carcinoma patients, HAEMATOLOG, 85(3), 2000, pp. 298-303
Citations number
46
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
HAEMATOLOGICA
ISSN journal
03906078 → ACNP
Volume
85
Issue
3
Year of publication
2000
Pages
298 - 303
Database
ISI
SICI code
0390-6078(200003)85:3<298:EACPCF>2.0.ZU;2-S
Abstract
Background and Objectives. The clinical and immunologic activities of inter leukin-2 (IL-2) in cancer patients have been extensively studied and descri bed; however, in most of these studies, IL-2 was administered by Intravenou s bolus or continuous infusion, white 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 o f IL-2, given at very low doses s.c. to patients with advanced renal cell c arcinoma (RCC), on a number of immunologic parameters: number of total lymp hocytes, number of CD4-, CD8-, CD25-positive cells, number of natural kille r (NK) cells, titers of IL-2 soluble receptor (slL-2R) and of C4, eosinophi ls, eosinophils cationic protein (ECP) and eosinophilic protein X (EPX). Fi nally, a logistic regression model was performed to identify early immunolo gic parameters that correlate with a favorable or unfavorable treatment out come. Results. Independently from the mere report of the changes induced by immun otherapy, the analysis showed that, within the pre-treatment model, a large eosinophil number predicts the failure of IL-2 treatment; in contrast, wit hin the post-treatment model, high C4 serum titers and, again, a large numb er of circulating eosinophils predict Immunotherapy failure. Interpretations and Conclusions. As far as concerns C4, its negative predic tive value could be related to the fact that It is an indirect index of mac rophage activation; thus, even though macrophages release substances with a ntitumor activity, they can also stimulate the release of slL-2R, which may compete for exogenous IL-2. Some authors have postulated that macrophages may even stimulate tumor cell growth, or impair Nh activity. Despite a grea t amount of uncertainty concerning the role of eosinophils, in our study, b lood eosinophilia predicts a poor response to immunotherapy In patients wit h advanced RCC, thus supporting previous observations from our own group. ( C) 2000, Ferrata Storti Foundation.