GM-CSF Production by Tumor Cells Is Associated with Improved Survival in Colorectal Cancer.
- Nebiker CA Authors' Affiliations: Department of Biomedicine, Institute for Surgical Research; Institute of Pathology, University of Basel; Department of Surgery, University Hospital, Basel; Ospedale Regionale, Lugano; Ospedale Regionale "San Giovanni," Bellinzona; Department of Surgery, Kantonsspital, St Gallen; Department of Surgery, Kantonsspital, Olten, Switzerland; Departments of General Surgery and Gastroenterology, Shanghai East Hospital, Tongji University, Shanghai, P.R. China; and Institute of Translational Pharmacology, National Research Council, Rome, Italy.
- Han J Authors' Affiliations: Department of Biomedicine, Institute for Surgical Research; Institute of Pathology, University of Basel; Department of Surgery, University Hospital, Basel; Ospedale Regionale, Lugano; Ospedale Regionale "San Giovanni," Bellinzona; Department of Surgery, Kantonsspital, St Gallen; Department of Surgery, Kantonsspital, Olten, Switzerland; Departments of General Surgery and Gastroenterology, Shanghai East Hospital, Tongji University, Shanghai, P.R. China; and Institute of Translational Pharmacology, National Research Council, Rome, ItalyAuthors' Affiliations: Department of Biomedicine, Institute for Surgical Research; Institute of Pathology, University of Basel; Department of Surgery, University Hospital, Basel; Ospedale Regionale, Lugano; Ospedale Regionale "San Giovanni," Bellinzona; Department of Surgery, Kantonsspital, St Gallen; Department of Surgery, Kantonsspital, Olten, Switzerland; Departments of General Surgery and Gastroenterology, Shanghai East Hospital, Tongji University, Shanghai, P.R. China; and Institute of Translational Pharmacology, National Research Council, Rome, ItalyAuthors' Affiliations: Department of Biomedicine, Institute for Surgical Research; Institute of Pathology, University of Basel; Department of Surgery, University Hospital, Basel; Ospedale Regionale, Lugano; Ospedale Regionale "San Giovanni," Bellinzona; Department of Surgery, Kantonsspital, St Gallen; Department of Surgery, Kantonsspital, Olten, Switzerland; Departments of General Surgery and Gastroenterology, Shanghai East Hospital, Tongji University, Shanghai, P.R. China; and Institute of Translational Pharmacology, National Research Council, Rome, Italy.
- Eppenberger-Castori S Authors' Affiliations: Department of Biomedicine, Institute for Surgical Research; Institute of Pathology, University of Basel; Department of Surgery, University Hospital, Basel; Ospedale Regionale, Lugano; Ospedale Regionale "San Giovanni," Bellinzona; Department of Surgery, Kantonsspital, St Gallen; Department of Surgery, Kantonsspital, Olten, Switzerland; Departments of General Surgery and Gastroenterology, Shanghai East Hospital, Tongji University, Shanghai, P.R. China; and Institute of Translational Pharmacology, National Research Council, Rome, Italy.
- Iezzi G Authors' Affiliations: Department of Biomedicine, Institute for Surgical Research; Institute of Pathology, University of Basel; Department of Surgery, University Hospital, Basel; Ospedale Regionale, Lugano; Ospedale Regionale "San Giovanni," Bellinzona; Department of Surgery, Kantonsspital, St Gallen; Department of Surgery, Kantonsspital, Olten, Switzerland; Departments of General Surgery and Gastroenterology, Shanghai East Hospital, Tongji University, Shanghai, P.R. China; and Institute of Translational Pharmacology, National Research Council, Rome, Italy.
- Hirt C Authors' Affiliations: Department of Biomedicine, Institute for Surgical Research; Institute of Pathology, University of Basel; Department of Surgery, University Hospital, Basel; Ospedale Regionale, Lugano; Ospedale Regionale "San Giovanni," Bellinzona; Department of Surgery, Kantonsspital, St Gallen; Department of Surgery, Kantonsspital, Olten, Switzerland; Departments of General Surgery and Gastroenterology, Shanghai East Hospital, Tongji University, Shanghai, P.R. China; and Institute of Translational Pharmacology, National Research Council, Rome, Italy.
- Amicarella F Authors' Affiliations: Department of Biomedicine, Institute for Surgical Research; Institute of Pathology, University of Basel; Department of Surgery, University Hospital, Basel; Ospedale Regionale, Lugano; Ospedale Regionale "San Giovanni," Bellinzona; Department of Surgery, Kantonsspital, St Gallen; Department of Surgery, Kantonsspital, Olten, Switzerland; Departments of General Surgery and Gastroenterology, Shanghai East Hospital, Tongji University, Shanghai, P.R. China; and Institute of Translational Pharmacology, National Research Council, Rome, Italy.
- Cremonesi E Authors' Affiliations: Department of Biomedicine, Institute for Surgical Research; Institute of Pathology, University of Basel; Department of Surgery, University Hospital, Basel; Ospedale Regionale, Lugano; Ospedale Regionale "San Giovanni," Bellinzona; Department of Surgery, Kantonsspital, St Gallen; Department of Surgery, Kantonsspital, Olten, Switzerland; Departments of General Surgery and Gastroenterology, Shanghai East Hospital, Tongji University, Shanghai, P.R. China; and Institute of Translational Pharmacology, National Research Council, Rome, Italy.
- Huber X Authors' Affiliations: Department of Biomedicine, Institute for Surgical Research; Institute of Pathology, University of Basel; Department of Surgery, University Hospital, Basel; Ospedale Regionale, Lugano; Ospedale Regionale "San Giovanni," Bellinzona; Department of Surgery, Kantonsspital, St Gallen; Department of Surgery, Kantonsspital, Olten, Switzerland; Departments of General Surgery and Gastroenterology, Shanghai East Hospital, Tongji University, Shanghai, P.R. China; and Institute of Translational Pharmacology, National Research Council, Rome, ItalyAuthors' Affiliations: Department of Biomedicine, Institute for Surgical Research; Institute of Pathology, University of Basel; Department of Surgery, University Hospital, Basel; Ospedale Regionale, Lugano; Ospedale Regionale "San Giovanni," Bellinzona; Department of Surgery, Kantonsspital, St Gallen; Department of Surgery, Kantonsspital, Olten, Switzerland; Departments of General Surgery and Gastroenterology, Shanghai East Hospital, Tongji University, Shanghai, P.R. China; and Institute of Translational Pharmacology, National Research Council, Rome, Italy.
- Padovan E Authors' Affiliations: Department of Biomedicine, Institute for Surgical Research; Institute of Pathology, University of Basel; Department of Surgery, University Hospital, Basel; Ospedale Regionale, Lugano; Ospedale Regionale "San Giovanni," Bellinzona; Department of Surgery, Kantonsspital, St Gallen; Department of Surgery, Kantonsspital, Olten, Switzerland; Departments of General Surgery and Gastroenterology, Shanghai East Hospital, Tongji University, Shanghai, P.R. China; and Institute of Translational Pharmacology, National Research Council, Rome, Italy.
- Angrisani B Authors' Affiliations: Department of Biomedicine, Institute for Surgical Research; Institute of Pathology, University of Basel; Department of Surgery, University Hospital, Basel; Ospedale Regionale, Lugano; Ospedale Regionale "San Giovanni," Bellinzona; Department of Surgery, Kantonsspital, St Gallen; Department of Surgery, Kantonsspital, Olten, Switzerland; Departments of General Surgery and Gastroenterology, Shanghai East Hospital, Tongji University, Shanghai, P.R. China; and Institute of Translational Pharmacology, National Research Council, Rome, Italy.
- Droeser RA Authors' Affiliations: Department of Biomedicine, Institute for Surgical Research; Institute of Pathology, University of Basel; Department of Surgery, University Hospital, Basel; Ospedale Regionale, Lugano; Ospedale Regionale "San Giovanni," Bellinzona; Department of Surgery, Kantonsspital, St Gallen; Department of Surgery, Kantonsspital, Olten, Switzerland; Departments of General Surgery and Gastroenterology, Shanghai East Hospital, Tongji University, Shanghai, P.R. China; and Institute of Translational Pharmacology, National Research Council, Rome, ItalyAuthors' Affiliations: Department of Biomedicine, Institute for Surgical Research; Institute of Pathology, University of Basel; Department of Surgery, University Hospital, Basel; Ospedale Regionale, Lugano; Ospedale Regionale "San Giovanni," Bellinzona; Department of Surgery, Kantonsspital, St Gallen; Department of Surgery, Kantonsspital, Olten, Switzerland; Departments of General Surgery and Gastroenterology, Shanghai East Hospital, Tongji University, Shanghai, P.R. China; and Institute of Translational Pharmacology, National Research Council, Rome, Italy.
- Rosso R Authors' Affiliations: Department of Biomedicine, Institute for Surgical Research; Institute of Pathology, University of Basel; Department of Surgery, University Hospital, Basel; Ospedale Regionale, Lugano; Ospedale Regionale "San Giovanni," Bellinzona; Department of Surgery, Kantonsspital, St Gallen; Department of Surgery, Kantonsspital, Olten, Switzerland; Departments of General Surgery and Gastroenterology, Shanghai East Hospital, Tongji University, Shanghai, P.R. China; and Institute of Translational Pharmacology, National Research Council, Rome, Italy.
- Bolli M Authors' Affiliations: Department of Biomedicine, Institute for Surgical Research; Institute of Pathology, University of Basel; Department of Surgery, University Hospital, Basel; Ospedale Regionale, Lugano; Ospedale Regionale "San Giovanni," Bellinzona; Department of Surgery, Kantonsspital, St Gallen; Department of Surgery, Kantonsspital, Olten, Switzerland; Departments of General Surgery and Gastroenterology, Shanghai East Hospital, Tongji University, Shanghai, P.R. China; and Institute of Translational Pharmacology, National Research Council, Rome, Italy.
- Oertli D Authors' Affiliations: Department of Biomedicine, Institute for Surgical Research; Institute of Pathology, University of Basel; Department of Surgery, University Hospital, Basel; Ospedale Regionale, Lugano; Ospedale Regionale "San Giovanni," Bellinzona; Department of Surgery, Kantonsspital, St Gallen; Department of Surgery, Kantonsspital, Olten, Switzerland; Departments of General Surgery and Gastroenterology, Shanghai East Hospital, Tongji University, Shanghai, P.R. China; and Institute of Translational Pharmacology, National Research Council, Rome, Italy.
- von Holzen U Authors' Affiliations: Department of Biomedicine, Institute for Surgical Research; Institute of Pathology, University of Basel; Department of Surgery, University Hospital, Basel; Ospedale Regionale, Lugano; Ospedale Regionale "San Giovanni," Bellinzona; Department of Surgery, Kantonsspital, St Gallen; Department of Surgery, Kantonsspital, Olten, Switzerland; Departments of General Surgery and Gastroenterology, Shanghai East Hospital, Tongji University, Shanghai, P.R. China; and Institute of Translational Pharmacology, National Research Council, Rome, Italy.
- Adamina M Authors' Affiliations: Department of Biomedicine, Institute for Surgical Research; Institute of Pathology, University of Basel; Department of Surgery, University Hospital, Basel; Ospedale Regionale, Lugano; Ospedale Regionale "San Giovanni," Bellinzona; Department of Surgery, Kantonsspital, St Gallen; Department of Surgery, Kantonsspital, Olten, Switzerland; Departments of General Surgery and Gastroenterology, Shanghai East Hospital, Tongji University, Shanghai, P.R. China; and Institute of Translational Pharmacology, National Research Council, Rome, Italy.
- Muraro MG Authors' Affiliations: Department of Biomedicine, Institute for Surgical Research; Institute of Pathology, University of Basel; Department of Surgery, University Hospital, Basel; Ospedale Regionale, Lugano; Ospedale Regionale "San Giovanni," Bellinzona; Department of Surgery, Kantonsspital, St Gallen; Department of Surgery, Kantonsspital, Olten, Switzerland; Departments of General Surgery and Gastroenterology, Shanghai East Hospital, Tongji University, Shanghai, P.R. China; and Institute of Translational Pharmacology, National Research Council, Rome, Italy.
- Mengus C Authors' Affiliations: Department of Biomedicine, Institute for Surgical Research; Institute of Pathology, University of Basel; Department of Surgery, University Hospital, Basel; Ospedale Regionale, Lugano; Ospedale Regionale "San Giovanni," Bellinzona; Department of Surgery, Kantonsspital, St Gallen; Department of Surgery, Kantonsspital, Olten, Switzerland; Departments of General Surgery and Gastroenterology, Shanghai East Hospital, Tongji University, Shanghai, P.R. China; and Institute of Translational Pharmacology, National Research Council, Rome, Italy.
- Zajac P Authors' Affiliations: Department of Biomedicine, Institute for Surgical Research; Institute of Pathology, University of Basel; Department of Surgery, University Hospital, Basel; Ospedale Regionale, Lugano; Ospedale Regionale "San Giovanni," Bellinzona; Department of Surgery, Kantonsspital, St Gallen; Department of Surgery, Kantonsspital, Olten, Switzerland; Departments of General Surgery and Gastroenterology, Shanghai East Hospital, Tongji University, Shanghai, P.R. China; and Institute of Translational Pharmacology, National Research Council, Rome, Italy.
- Sconocchia G Authors' Affiliations: Department of Biomedicine, Institute for Surgical Research; Institute of Pathology, University of Basel; Department of Surgery, University Hospital, Basel; Ospedale Regionale, Lugano; Ospedale Regionale "San Giovanni," Bellinzona; Department of Surgery, Kantonsspital, St Gallen; Department of Surgery, Kantonsspital, Olten, Switzerland; Departments of General Surgery and Gastroenterology, Shanghai East Hospital, Tongji University, Shanghai, P.R. China; and Institute of Translational Pharmacology, National Research Council, Rome, Italy.
- Zuber M Authors' Affiliations: Department of Biomedicine, Institute for Surgical Research; Institute of Pathology, University of Basel; Department of Surgery, University Hospital, Basel; Ospedale Regionale, Lugano; Ospedale Regionale "San Giovanni," Bellinzona; Department of Surgery, Kantonsspital, St Gallen; Department of Surgery, Kantonsspital, Olten, Switzerland; Departments of General Surgery and Gastroenterology, Shanghai East Hospital, Tongji University, Shanghai, P.R. China; and Institute of Translational Pharmacology, National Research Council, Rome, Italy.
- Tornillo L Authors' Affiliations: Department of Biomedicine, Institute for Surgical Research; Institute of Pathology, University of Basel; Department of Surgery, University Hospital, Basel; Ospedale Regionale, Lugano; Ospedale Regionale "San Giovanni," Bellinzona; Department of Surgery, Kantonsspital, St Gallen; Department of Surgery, Kantonsspital, Olten, Switzerland; Departments of General Surgery and Gastroenterology, Shanghai East Hospital, Tongji University, Shanghai, P.R. China; and Institute of Translational Pharmacology, National Research Council, Rome, Italy.
- Terracciano L Authors' Affiliations: Department of Biomedicine, Institute for Surgical Research; Institute of Pathology, University of Basel; Department of Surgery, University Hospital, Basel; Ospedale Regionale, Lugano; Ospedale Regionale "San Giovanni," Bellinzona; Department of Surgery, Kantonsspital, St Gallen; Department of Surgery, Kantonsspital, Olten, Switzerland; Departments of General Surgery and Gastroenterology, Shanghai East Hospital, Tongji University, Shanghai, P.R. China; and Institute of Translational Pharmacology, National Research Council, Rome, Italy giulio.spagnoli@usb.ch lterracciano@uhbs.ch.
- Spagnoli GC Authors' Affiliations: Department of Biomedicine, Institute for Surgical Research; Institute of Pathology, University of Basel; Department of Surgery, University Hospital, Basel; Ospedale Regionale, Lugano; Ospedale Regionale "San Giovanni," Bellinzona; Department of Surgery, Kantonsspital, St Gallen; Department of Surgery, Kantonsspital, Olten, Switzerland; Departments of General Surgery and Gastroenterology, Shanghai East Hospital, Tongji University, Shanghai, P.R. China; and Institute of Translational Pharmacology, National Research Council, Rome, Italy giulio.spagnoli@usb.ch lterracciano@uhbs.ch.
- 2014-04-17
Published in:
- Clinical cancer research : an official journal of the American Association for Cancer Research. - 2014
Adult
Aged
Aged, 80 and over
Biomarkers, Tumor
Case-Control Studies
Cell Proliferation
Chemokines
Colorectal Neoplasms
Cytokines
Female
Follow-Up Studies
Gene Expression Profiling
Granulocyte-Macrophage Colony-Stimulating Factor
Humans
Immunocompetence
Immunoenzyme Techniques
Macrophage Colony-Stimulating Factor
Macrophages
Male
Middle Aged
Monocytes
Neoplasm Grading
Neoplasm Invasiveness
Neoplasm Staging
Prognosis
Real-Time Polymerase Chain Reaction
Survival Rate
Tissue Array Analysis
English
PURPOSE
Colorectal cancer infiltration by CD16(+) myeloid cells correlates with improved prognosis. We addressed mechanistic clues and gene and protein expression of cytokines potentially associated with macrophage polarization.
EXPERIMENTAL DESIGN
GM-CSF or M-CSF-stimulated peripheral blood CD14(+) cells from healthy donors were cocultured with colorectal cancer cells. Tumor cell proliferation was assessed by (3)H-thymidine incorporation. Expression of cytokine genes in colorectal cancer and autologous healthy mucosa was tested by quantitative, real-time PCR. A tumor microarray (TMA) including >1,200 colorectal cancer specimens was stained with GM-CSF- and M-CSF-specific antibodies. Clinicopathological features and overall survival were analyzed.
RESULTS
GM-CSF induced CD16 expression in 66% ± 8% of monocytes, as compared with 28% ± 1% in cells stimulated by M-CSF (P = 0.011). GM-CSF but not M-CSF-stimulated macrophages significantly (P < 0.02) inhibited colorectal cancer cell proliferation. GM-CSF gene was expressed to significantly (n = 45, P < 0.0001) higher extents in colorectal cancer than in healthy mucosa, whereas M-CSF gene expression was similar in healthy mucosa and colorectal cancer. Accordingly, IL1β and IL23 genes, typically expressed by M1 macrophages, were expressed to significantly (P < 0.001) higher extents in colorectal cancer than in healthy mucosa. TMA staining revealed that GM-CSF production by tumor cells is associated with lower T stage (P = 0.02), "pushing" growth pattern (P = 0.004) and significantly (P = 0.0002) longer survival in mismatch-repair proficient colorectal cancer. Favorable prognostic effect of GM-CSF production by colorectal cancer cells was confirmed by multivariate analysis and was independent from CD16(+) and CD8(+) cell colorectal cancer infiltration. M-CSF expression had no significant prognostic relevance.
CONCLUSIONS
GM-CSF production by tumor cells is an independent favorable prognostic factor in colorectal cancer.
Colorectal cancer infiltration by CD16(+) myeloid cells correlates with improved prognosis. We addressed mechanistic clues and gene and protein expression of cytokines potentially associated with macrophage polarization.
EXPERIMENTAL DESIGN
GM-CSF or M-CSF-stimulated peripheral blood CD14(+) cells from healthy donors were cocultured with colorectal cancer cells. Tumor cell proliferation was assessed by (3)H-thymidine incorporation. Expression of cytokine genes in colorectal cancer and autologous healthy mucosa was tested by quantitative, real-time PCR. A tumor microarray (TMA) including >1,200 colorectal cancer specimens was stained with GM-CSF- and M-CSF-specific antibodies. Clinicopathological features and overall survival were analyzed.
RESULTS
GM-CSF induced CD16 expression in 66% ± 8% of monocytes, as compared with 28% ± 1% in cells stimulated by M-CSF (P = 0.011). GM-CSF but not M-CSF-stimulated macrophages significantly (P < 0.02) inhibited colorectal cancer cell proliferation. GM-CSF gene was expressed to significantly (n = 45, P < 0.0001) higher extents in colorectal cancer than in healthy mucosa, whereas M-CSF gene expression was similar in healthy mucosa and colorectal cancer. Accordingly, IL1β and IL23 genes, typically expressed by M1 macrophages, were expressed to significantly (P < 0.001) higher extents in colorectal cancer than in healthy mucosa. TMA staining revealed that GM-CSF production by tumor cells is associated with lower T stage (P = 0.02), "pushing" growth pattern (P = 0.004) and significantly (P = 0.0002) longer survival in mismatch-repair proficient colorectal cancer. Favorable prognostic effect of GM-CSF production by colorectal cancer cells was confirmed by multivariate analysis and was independent from CD16(+) and CD8(+) cell colorectal cancer infiltration. M-CSF expression had no significant prognostic relevance.
CONCLUSIONS
GM-CSF production by tumor cells is an independent favorable prognostic factor in colorectal cancer.
- Language
-
- English
- Open access status
- bronze
- Identifiers
-
- DOI 10.1158/1078-0432.CCR-13-2774
- PMID 24737547
- Persistent URL
- https://sonar.ch/global/documents/101986
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