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