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

Abstract

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% AE 8% of monocytes, as compared with 28% AE 1% in cells stimulated by M-CSF (P ¼ 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 ¼ 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, IL1b 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 ¼ 0.02), "pushing" growth pattern (P ¼ 0.004) and significantly (P ¼ 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 þ and CD8 þ 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. Clin Cancer Res; 20(12); 3094-106. Ó2014 AACR.

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PKCα in colon cancer cells promotes M1 macrophage polarization via MKK3/6‐P38 MAPK pathway

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