We are very glad to inform you that the Laboratory of Translational Cancer Genomics will start new project awarded by Czech Health Research Council. The project will be carried out in cooperation with the University Hospital in Pilsen and Institute of Experimental Medicine Czech Academy of Sciences.
NU21-03-00506: Tumor cell and mutational landscape in colorectal cancer development
Principal Investigator: Kari Hemminki, M.D., Ph.D. (Faculty of medicine CUNI)
Co-investigator: prof. MUDr. Václav Liška, Ph.D. (University hospital in Pilsen)
Co-investigator: MUDr. Pavel Vodička, CSc. (IEM CAS)
Date of implementation: 1.5.2021 – 31.12.2024
Abstract:
Cancer growth and spread is controlled by tumor microenvironment, which is composed of immune and other cell types, also found in chronic inflammatory processes. Recently, a survival prediction tool, the immunoscore, was introduced for colorectal cancer (CRC), based on quantification of two tumor suppressive immune T cells (CD3+ and CD8+) in the primary tumor. The immunoscore was shown to provide a better prognostic prediction than the traditional TNM classification. However, the immunoscore did not consider metastatic (stage IV) CRC patients who are known to have the worst prognosis and are, therefore, in an urgent need of prognostic assessment. The development of prognostic tools for CRC is hampered by the lack of large sample sets covering normal colon tissue, primary tumor and metastasis from the same individual. We aim to reconsider the use of tumor microenvironment in the assessment of CRC prognosis and will also include metastatic patients in the development of a prognostic tool, based on cellular composition of 11 cell types. We will add a novel marker – telomere length – measured in defined tissue compartments, as the telomere length is associated in many carcinogenic processes. The sample set available for this study is internationally unique, including 160 patients for whom samples of normal colonic mucosa, primary tumor and liver metastasis will be obtained. A half of these patients presented with liver metastases at diagnosis (stage IV) while the other half developed metastases up to years later (stages II/III). This study will outline, for the first time, immune-cell landscape in the same patients from normal mucosa to primary CRC and further to liver metastasis in terms of cell type distribution and telomere length. The cell types include CD3+ and CD8+, and 9 other cell types, with which we intend to further refine the immunoscore, and, possibly a telomere-length-based score. Most importantly, we will devise predictive tools also for metastatic CRCs.
We are looking for this collaboration!