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

The in: situ function of tumour-infiltrating leukocytes (TIL) in human colo rectal adenocarcinoma (CRC) is unclear, Local cytokine expression probably regulates the anti-tumour immune response and tumour immune surveillance. W e 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 prim ary CRC, using a semiquantitative RT-PCR, Lamina propria-infiltrating leuko cytes (LPL) and epithelial cells from normal colon mucosa of 10 CRC patient s served as negative controls. Median levels of IFN-gamma and TNF-alpha mRN A were higher in TIL than LPL (p = 0.0002 and 0.0001). IL-10 mRNA was gener ally observed in TIL and LPL, but no or very small amounts of IL-4 transcri pts were detected in TIL and LPL, TNF-alpha and IL-10 mRNA were more abunda nt in colorectal tumour cells than in the normal epithelial cells (p = 0.01 36 and 0,0036), The number of IFN-gamma transcripts in TIL correlated negat ively (p = 0.039) and the number of TNF-alpha transcripts in tumour cells c orrelated positively with the Dukes' stages (p = 0.0147), Our results sugge st that TIL are characterized by a type 1 (Th1/Tc1-like) pattern of cytokin e expression and function as T cells land macrophages) in the local, cell-m ediated antitumour immune response in early stages of CRC, Changes in IFN-g amma 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.