Immune Infiltrates In Liver Metastases Of Colorectal Cancer And Response To Chemotherapy

e15069 Background: Colorectal cancer (CRC) is a major cause of death from cancer. Patients with irresectable or metastasized CRC usually receive chemotherapy in combination with a monoclonal antibody, median overall survival time is around 20- 21 months with response rates of around 50%. Almost half of the patients experience treatment related side effects without benefit. K-ras mutation is the only (negative) predictive marker for response to therapy (for EGFR-targeting antibody treatment), no biomarkers are available that help to select patients most likely responding to chemotherapy. In primary colon cancer immune infiltrates in the tumor represent an important prognostic factor. High densities of tumor infiltrating lymphocytes (TIL) were shown to be correlated with an improved survival in patients with primary CRC. TILs therefore represent a valuable prognostic tool, a high density of immune cells being associated with good outcome independently of other established prognostic markers. Little is known about an association between these immune cells and the response to chemotherapy. Methods: Here the relation between infiltrates of immune cells in liver metastases of CRC and the response to chemotherapy (using immunohistochemical staining against CD8, GranB, FOXP3, CD45RO, etc.) was investigated. Samples from 33 patients with metastasized colorectal cancer (samples from 22 patients were used as training set and samples from 11 patients as validation set) were analyzed. Results: The evaluation of positively stained TIL in the invasive margin of the liver metastasis allowed to predict response to chemotherapy. This was also observed in the analysis of the time to progression, where higher numbers of positively stained cells were associated with longer intervals. The difference between the groups with either response or no response to chemotherapy in time to progression was statistically significant in the analyzed sets (Mann-Whitney- U, p<0.001, two-tailed, z=-3,961, n=33). In primary tumors no association between TIL densities and response to chemotherapy was observed. Conclusions: Our results suggest that the immune system has an important impact on the efficacy of chemotherapy and the presented data will have implications for the assessment of therapy options. No significant financial relationships to disclose.