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.
BACKGROUND AND OBJECTIVE: The clinical and immunologic activities of interleukin-2 (IL-2) in cancerpatients 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.
Authors: Carly E Whyte; Kailash Singh; James Dooley; Oliver T Burton; Meryem Aloulou; Lubna Kouser; Rafael Valente Veiga; Amy Dashwood; Hanneke Okkenhaug; Samira Benadda; Alena Moudra; Orian Bricard; Stephanie Lienart; Pascal Bielefeld; Carlos P Roca; Francisco José Naranjo-Galindo; Félix Lombard-Vadnais; Steffie Junius; David Bending; Masahiro Ono; Tino Hochepied; Timotheus Y F Halim; Susan Schlenner; Sylvie Lesage; Adrian Liston Journal: J Exp Med Date: 2022-06-14 Impact factor: 17.579
Authors: C Nicole Rosenzweig; Zhen Zhang; Xiaer Sun; Lori J Sokoll; Katherine Osborne; Alan W Partin; Daniel W Chan Journal: J Urol Date: 2009-01-20 Impact factor: 7.450
Authors: Anam Tariq; Keisuke Okamato; Azka Tariq; Avi Z Rosenberg; Karim M Soliman; David W Ploth; Mohamed G Atta; Blaithin A McMahon Journal: BMC Nephrol Date: 2020-01-13 Impact factor: 2.388
Authors: In Gab Jeong; Kyung Seok Han; Jae Young Joung; Woo Suk Choi; Seung Sik Hwang; Seung Ok Yang; Ho Kyung Seo; Jinsoo Chung; Kang Hyun Lee Journal: J Korean Med Sci Date: 2007-09 Impact factor: 2.153