Comprehensive Immune-landscape in Localized Colorectal Cancer

Colorectal Cancer, Immune Landscape

Surgery still remains the mainstay of treatment for localized colorectal cancer. However, nearly 30% of patients with localized colorectal cancer (stage II and stage III) will present with recurrence. Tumor progression is mediated by both intrinsic genetic changes and by extrinsic epigenetic and host environmental factors, including interactions with the immune system. Several studies demonstrated that tumor infiltrating memory T-cells and type, density and location of infiltrating T cells are better predictors of disease-free survival in patients with CRC compared to the standard TNM staging. These data suggest that tumor invasion and progression are more accurately predicted by immune response in the primary tumor. In addition, mismatch repair (MMR)-deficient tumors are characterized a priori by a higher frequency of tumor infiltrating lymphocytes and are associated with significantly improved prognosis. Recently, Stotz et al showed that the preoperative lymphocyte to monocyte ratio in peripheral blood samples predicts clinical outcome in patients with stage III colon cancer. So far there is no comprehensive analysis of the immune-landscape in CRC. The aim of the current project is to identify a comprehensive panel of immunomarkers in localized colorectal cancer (stage II and stage III) applicable for the detection of patients at high risk of recurrence. For the first time, specific tumor-infiltrating immune cells, mismatch repair protein expression in tumor tissue and preoperative blood based inflammatory markers from routine blood counts in corresponding peripheral blood samples and known clinicopathological features will be correlated with outcome in 300 localized CRC patients.

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