GM-CSF Production by Tumor Cells Is Associated with Improved Survival in Colorectal Cancer

Nebiker, Christian A. and Han, Junyi and Eppenberger-Castori, Serenella and Iezzi, Giandomenica and Hirt, Christian and Amicarella, Francesca and Cremonesi, Eleonora and Huber, Xaver and Padovan, Elisabetta and Angrisani, Basilio and Droeser, Raoul A. and Rosso, Raffaele and Bolli, Martin and Oertli, Daniel and von Holzen, Urs and Adamina, Michel and Muraro, Manuele G. and Mengus, Chantal and Zajac, Paul and Sconocchia, Giuseppe and Zuber, Markus and Tornillo, Luigi and Terracciano, Luigi and Spagnoli, Giulio C.. (2014) GM-CSF Production by Tumor Cells Is Associated with Improved Survival in Colorectal Cancer. Clinical cancer research : a journal of clinical and translational research, 20 (12). pp. 3094-3106.

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Official URL: https://edoc.unibas.ch/61940/

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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, IL1beta 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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Cancer Immunotherapy (Iezzi)
UniBasel Contributors:Iezzi, Giandomenica
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Association for Cancer Research
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:27 Jul 2020 14:38
Deposited On:27 Jul 2020 14:38

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