Characterisation of cytokine mRNA expression in tumour-infiltrating mononuclear cells and tumour cells freshly isolated from human colorectal carcinomas

Abstract

The in situ function of tumour-infiltrating leukocytes (TIL) in human colorectal adenocarcinoma (CRC) is unclear. Local cytokine expression probably regulates the anti-tumour immune response and tumour immune surveillance. We examined the distribution of mRNA for IFN-gamma, TNF-alpha, IL-10 and IL-4 in TIL, and tumour cells freshly isolated from 21 surgically removed primary CRC, using a semiquantitative RT-PCR. Lamina propria-infiltrating leukocytes (LPL) and epithelial cells from normal colon mucosa of 10 CRC patients served as negative controls. Median levels of IFN-gamma and TNF-alpha mRNA were higher in TIL than LPL (p = 0.0002 and 0.0001). IL-10 mRNA was generally observed in TIL and LPL, but no or very small amounts of IL-4 transcripts were detected in TIL and LPL. TNF-alpha and IL-10 mRNA were more abundant in colorectal tumour cells than in the normal epithelial cells (p = 0.0136 and 0.0036). The number of IFN-gamma transcripts in TIL correlated negatively (p = 0.039) and the number of TNF-alpha transcripts in tumour cells correlated positively with the Dukes' stages (p = 0.0147). Our results suggest that TIL are characterized by a type 1 (Th1/Tc1-like) pattern of cytokine expression and function as T cells (and macrophages) in the local, cell-mediated anti-tumour immune response in early stages of CRC. Changes in IFN-gamma and TNF-alpha mRNA in TIL and tumour cells could be related to tumour progress (e.g. by T cell anergy) or forming of metastases, respectively.