Cytokine secretion associated with the clearance of apoptotic bodies in renal cell carcinoma patients

The factors determining the outcome of immunotherapy in metastatic renal ce ll carcinoma (RCC) patients remain elusive. Macrophages from normal donors that phagocytose apoptotic cells secrete the immunosuppressive cytokine IL- 10 in vitro. Conversely, IL-10 genetic deletion enhances the immunogenicity of apoptotic tumor cells in vivo. Elevated pre-treatment levels of IL-10 a re associated with an unfavorable outcome of RCC, We examined whether the a bility to release IL-10 by macrophages from RCC patients that phagocytosed apoptotic cells correlated with the outcome of immunotherapy. To this aim, we derived macrophages from 30 patients with metastatic RCC and from 21 hea lthy subjects (II sex- and age-matched healthy controls and 10 younger dono rs). Patients either had a clinical response after immunotherapy, with a me dian survival after treatment of more than 18 months (n = 16), or were begi nning immunotherapy after diagnosis of metastatic disease (n = 14). Macroph ages from responding patients challenged with apoptotic cells released sign ificantly less IL-10 than controls (p = 0.0075) and recently diagnosed pati ents (p = 0.0198), as ascertained by a 2-sided Student's t-test, This was n ot because macrophages from responding patients lost: the ability to secret e IL-10, because antibody opsonization of apoptotic cells rescued IL-10 sec retion. In contrast, macrophages from all groups of donors released similar amounts of TNF-alpha, The failure in IL-10 secretion by engulfing macropha ges of responding subjects may exalt the immunogenicity of dying tumor cell s, contributing to the success of immunotherapy. (C) 2001 Wiley-Liss, Inc.