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

Haematologica. 2000 Mar;85(3):298-303.

Abstract

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.

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Renal Cell / diagnosis
  • Carcinoma, Renal Cell / drug therapy*
  • Complement C4 / metabolism*
  • Eosinophils / cytology*
  • Female
  • Humans
  • Immunotherapy
  • Injections, Subcutaneous
  • Interferons / administration & dosage*
  • Interferons / blood
  • Interleukin-2 / administration & dosage*
  • Interleukin-2 / blood
  • Kidney Neoplasms / diagnosis
  • Kidney Neoplasms / drug therapy*
  • Logistic Models
  • Lymphocytes / cytology
  • Male
  • Middle Aged
  • Prognosis
  • Receptors, Interleukin-2 / blood
  • Solubility
  • T-Lymphocyte Subsets / cytology
  • Treatment Outcome

Substances

  • Complement C4
  • Interleukin-2
  • Receptors, Interleukin-2
  • Interferons