Distinct changes of dendritic cell number and IL-12 mRNA level in adjacent mucosa throughout the colorectal adenoma-carcinoma sequence.
Adjacent mucosa may reflect the conflicting of host factors in response to the establishment or invasion of cancers. Characterization of anti-tumor immunity in this region may add help in understanding the immune-related mechanisms of colorectal carcinoma (CRC). In this study, adjacent non-tumor mucosa from 36 patients with colorectal adenoma (CRA), 26 with CRC and normal mucosa from 15 health controls were included, immune cell populations of dendritic cell, lymphocyte and macrophage were characterized with immunohistochemistry (IHC) and tissue messenger RNA (mRNA) levels of Th1 cytokines interferon (IFN)-gamma and its upstream inducers interleukin (IL)-12 and IL-18 were quantified with real-time PCR; In addition, dendritic cell differentiation and function inhibitors cyclooxygenase-2 (COX-2) and IL-6 mRNA levels were also quantified. By IHC, a significant decreased dendritic cell density in the non-tumor mucosa adjacent to CRC was detected (P < 0.05) as compared to the normal controls or adjacent mucosa of CRA. The grading scores for lymphocyte number in the adjacent mucosa of CRA and CRC were gradually non-statistically increased, while the grading scores for macrophages number was not changed. By quantitative real-time PCR, distinct local cytokine gene expression profile was demonstrated. In which, the Th1 cytokines, particularly IL-12, were increased in adjacent mucosa of CRA, but all significantly decreased in adjacent mucosa of CRC. In addition, the mRNA levels of IL-6 and COX-2 were significantly higher in adjacent mucosa of CRC than that in adjacent mucosa of CRA (both P < 0.05). Therefore, dendritic cell functional changes could be one of the important mechanisms for altered anti-tumour immunity in the adjacent non-tumor mucosa throughout adenoma-carcinoma sequence. The increased COX-2 and IL-6 might contribute to dendritic cell functional defect in adjacent mucosa of CRC.
Cui
Guanglin
G
Laboratory of Gastroenterology, Institute of Clinical Medicine, Faculty of Medicine, University of Tromsø, Tromsø 9037, Norway. guanglin.cui@fagmed.uit.no
Yuan
Aping
A
Goll
Rasmus
R
Olsen
Trine
T
Husebekk
Anne
A
Vonen
Barthold
B
Florholmen
Jon
J
D000236:Adenoma / Q000276:immunology* / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology; D002277:Carcinoma / Q000276:immunology* / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000473:pathology*; D003713:Dendritic Cells / Q000166:cytology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D018664:Interleukin-12 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
D000970:Antineoplastic Agents; D012333:RNA, Messenger; D018664:Interleukin-12