Abstract
The factors determining the outcome of immunotherapy in metastatic renal cell 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 are associated with an unfavorable outcome of RCC. We examined whether the ability 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 healthy subjects (11 sex- and age-matched healthy controls and 10 younger donors). Patients either had a clinical response after immunotherapy, with a median survival after treatment of more than 18 months (n = 16), or were beginning immunotherapy after diagnosis of metastatic disease (n = 14). Macrophages from responding patients challenged with apoptotic cells released significantly less IL-10 than controls (p = 0.0075) and recently diagnosed patients (p = 0.0198), as ascertained by a 2-sided Student's t-test. This was not because macrophages from responding patients lost the ability to secrete IL-10, because antibody opsonization of apoptotic cells rescued IL-10 secretion. In contrast, macrophages from all groups of donors released similar amounts of TNF-α. The failure in IL-10 secretion by engulfing macrophages of responding subjects may exalt the immunogenicity of dying tumor cells, contributing to the success of immunotherapy.
| Original language | English |
|---|---|
| Pages (from-to) | 713-717 |
| Number of pages | 5 |
| Journal | International Journal of Cancer |
| Volume | 91 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Mar 1 2001 |
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Keywords
- Apoptosis
- IL-10
- Immunotherapy
- Phagocytosis
- Renal cell carcinoma
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Cytokine secretion associated with the clearance of apoptotic bodies in renal cell carcinoma patients. / Bondanza, Attilio; Rovere, Patrizia; Borri, Anna; Caremoli, Elena Rota; Guidetti, Anna; Citterio, Giovanni; Consogno, Giuseppe; Zimmermann, Valérie S.; Rugarli, Claudio; Manfredi, Angelo A.
In: International Journal of Cancer, Vol. 91, No. 5, 01.03.2001, p. 713-717.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cytokine secretion associated with the clearance of apoptotic bodies in renal cell carcinoma patients
AU - Bondanza, Attilio
AU - Rovere, Patrizia
AU - Borri, Anna
AU - Caremoli, Elena Rota
AU - Guidetti, Anna
AU - Citterio, Giovanni
AU - Consogno, Giuseppe
AU - Zimmermann, Valérie S.
AU - Rugarli, Claudio
AU - Manfredi, Angelo A.
PY - 2001/3/1
Y1 - 2001/3/1
N2 - The factors determining the outcome of immunotherapy in metastatic renal cell 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 are associated with an unfavorable outcome of RCC. We examined whether the ability 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 healthy subjects (11 sex- and age-matched healthy controls and 10 younger donors). Patients either had a clinical response after immunotherapy, with a median survival after treatment of more than 18 months (n = 16), or were beginning immunotherapy after diagnosis of metastatic disease (n = 14). Macrophages from responding patients challenged with apoptotic cells released significantly less IL-10 than controls (p = 0.0075) and recently diagnosed patients (p = 0.0198), as ascertained by a 2-sided Student's t-test. This was not because macrophages from responding patients lost the ability to secrete IL-10, because antibody opsonization of apoptotic cells rescued IL-10 secretion. In contrast, macrophages from all groups of donors released similar amounts of TNF-α. The failure in IL-10 secretion by engulfing macrophages of responding subjects may exalt the immunogenicity of dying tumor cells, contributing to the success of immunotherapy.
AB - The factors determining the outcome of immunotherapy in metastatic renal cell 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 are associated with an unfavorable outcome of RCC. We examined whether the ability 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 healthy subjects (11 sex- and age-matched healthy controls and 10 younger donors). Patients either had a clinical response after immunotherapy, with a median survival after treatment of more than 18 months (n = 16), or were beginning immunotherapy after diagnosis of metastatic disease (n = 14). Macrophages from responding patients challenged with apoptotic cells released significantly less IL-10 than controls (p = 0.0075) and recently diagnosed patients (p = 0.0198), as ascertained by a 2-sided Student's t-test. This was not because macrophages from responding patients lost the ability to secrete IL-10, because antibody opsonization of apoptotic cells rescued IL-10 secretion. In contrast, macrophages from all groups of donors released similar amounts of TNF-α. The failure in IL-10 secretion by engulfing macrophages of responding subjects may exalt the immunogenicity of dying tumor cells, contributing to the success of immunotherapy.
KW - Apoptosis
KW - IL-10
KW - Immunotherapy
KW - Phagocytosis
KW - Renal cell carcinoma
UR - http://www.scopus.com/inward/record.url?scp=0035283741&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035283741&partnerID=8YFLogxK
U2 - 10.1002/1097-0215(200002)9999:9999<::AID-IJC1096>3.0.CO;2-G
DO - 10.1002/1097-0215(200002)9999:9999<::AID-IJC1096>3.0.CO;2-G
M3 - Article
C2 - 11267985
AN - SCOPUS:0035283741
VL - 91
SP - 713
EP - 717
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 5
ER -