Kobaek-Larsen M, Diederichsen A, Agger R, Nissen I, Hokland M, Zeuthen J, Ritskes-Hoitinga J. Immunohistochemical characterisation of the local immune response in azoxymethane-induced colon tumours in the BDIX inbred rat strain. APMIS 2004;112:698–707. The aim of the present study was to characterise the local immune response in a chemically induced colon tumour model in the rat. Elucidating the character of the immune reaction may contribute to optimizing immunotherapeutic regimens for colon carcinoma in this model. Colon cancer was induced by four weekly subcutaneous azoxymethane injections in inbred rats of the BDIX/OrlIco strain in two separate studies. Azoxymethane-induced tumours show many similarities to spontaneously occurring human colon carcinomas with respect to histopathological appearance. In our studies, the overall inflammatory reaction of the submucosa below the tumour was evaluated in haematoxylin-eosin-stained tissue sections. Phenotypic characterization of leukocyte infiltration in the tumour tissue was performed by immunohistochemical staining using antibodies detecting various leukocyte subsets, i.e. T cells, natural killer cells, macrophages/monocytes, and dendritic cells. The results showed that the azoxymethane-induced colon tumours were strongly infiltrated by macrophages. Furthermore, the tumours showed a moderate degree of infiltrating CD4-positive cells. Very few natural killer, CD8-positive T cells and dendritic cells (identified by the OX62 antibody) were seen in the tumour tissue. Virtually no CD25-positive cells were found. This immunohistochemical characterisation of the tumour-infiltrating immune response in this rat model could form the basis for studies aimed at developing new immunotherapeutic regimens for human colon cancer.
Biomedical Laboratory, University of Southern Denmark, Odense, 2:
Institute of Medical Microbiology & Immunology, University of Aarhus, Aarhus, and 3:
Danish Cancer Society, Copenhagen, Denmark