Grimm et al. BMC Cancer 2010, 10:82 http://www.biomedcentral.com/1471-2407/10/82 R E S E A R C H A R T I C L E Open Access Evaluation of immunological escape mechanisms in a mouse model of colorectal liver metastases Martin Grimm2, Martin Gasser1, Marco Bueter1, Johanna Strehl2, Johann Wang2, Ekaterina Nichiporuk2, Detlef Meyer3, Christoph T Germer1, Ana M Waaga-Gasser2*, Andreas Thalheimer1 Abstract Background: The local and systemic activation and regulation of the immune system by malignant cells during carcinogenesis is highly complex with involvement of the innate and acquired immune system. Despite the fact that malignant cells do have antigenic properties their immunogenic effects are minor suggesting tumor induced mechanisms to circumvent cancer immunosurveillance. The aim of this study is the analysis of tumor immune escape mechanisms in a colorectal liver metastases mouse model at different points in time during tumor growth. Methods: CT26.WT murine colon carcinoma cells were injected intraportally in Balb/c mice after median laparotomy using a standardized injection technique. Metastatic tumor growth in the liver was examined by standard histological procedures at defined points in time during metastatic growth. Liver tissue with metastases was additionally analyzed for cytokines, T cell markers and Fas/Fas-L expression using immunohistochemistry, immunofluorescence and RT-PCR. Comparisons were performed by analysis of variance or paired and unpaired t test when appropriate. Results: Intraportal injection of colon carcinoma cells resulted in a gradual and time dependent metastatic growth. T cells of regulatory phenotype (CD4+CD25+Foxp3+) which might play a role in protumoral immune response were found to infiltrate peritumoral tissue increasingly during carcinogenesis. Expression of cytokines IL-10, TGF-b and TNF-a were increased during tumor growth whereas IFN-g showed a decrease of the expression from day 10 on following an initial increase. Moreover, liver metastases of murine colon carcinoma show an up-regulation of FAS-L on tumor cell surface with a decreased expression of FAS from day 10 on. CD8+ T cells express FAS and show an increased rate of apoptosis at perimetastatic location. Conclusions: This study describes cellular and macromolecular changes contributing to immunological escape mechanisms during metastatic growth in a colorectal liver metastases mouse model simulating the situation in human cancer. Background Colorectal carcinoma is the third most common cause of cancer-related deaths worldwide. Although great pro- ceedings have been made in diagnosis and treatment, still 40-50% of colorectal cancer patients die of the dis- ease within five years of diagnosis [1]. Formation of hepatic metastases in colorectal cancer is associated with poor prognosis, resulting in the death of more than 80% of patients over the long-term [2]. Surgery is the primary treatment option for isolated metastases, but * Correspondence: waaga-gasser@chirurgie.uni-wuerzburg.de 2Department of General Surgery, Molecular Oncology and Immunology, University of Wuerzburg Hospital, Germany only 20% to 25% of patients displaying hepatic metas- tases are suitable for resection and recurrence after sur- gical therapy is frequent [3]. Therefore, the development of new treatment modalities for liver metastases of col- orectal cancer is urgently needed. Particularly with regard to therapeutic modification of the immune sys- tem, understanding of tumor-specific immunological responses and mechanisms leading to induction or sup- pression of the immune system are required. The local and systemic activation and regulation of the immune system by malignant cells during carcino- genesis is highly complex with involvement of the innate and acquired immune system [4]. Despite the fact that malignant cells do have antigenic properties their © 2010 Grimm et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.