Microbiome, Immune-system and Tumor Interaction in Colorectal Cancer

Colorectal cancer (CRC) is the second leading cause of cancer-related mortality. Despite the improvement of surgical techniques, \~30-50% of patients with locoregional CRC who undergo potentially curative surgery ultimately relapse and die of metastatic disease. On the other hand, it is also well established that adjuvant systemic chemotherapy can decrease the risk of death in these patients. Currently, the standard treatment of locoregional CRC is based on curative surgery alone or followed by adjuvant systemic chemotherapy based on risk factors. In this regard, international guidelines recommend chemotherapy for stage III and stage II colon cancer with high risk prognostic characteristics, including T4 lesions, poorly differentiated tumors, lymphovascular or perineural invasion, tumour presentation with obstruction or tumour perforation, positive margins, and inadequate (\<12) number of lymph nodes analyzed after surgery. In patients treated with surgery and adjuvant systemic chemotherapy the 3-year disease-free survival (3y DFS) is 72% in stage III patients and 87% in stage II patients.The risk factors known to date do not always correctly predict the prognosis in these patients. For example, tumors of the same stage can largely differ in both prognosis, which can lead to wrong treatment decisions. This means that our knowledge about factors influencing the chance of recurrence and the prediction of benefit from systemic treatment is limited. Identification of these factors along with better treatment strategies may help in reducing the recurrence rate and raising the life expectancy of CRC patients. In this regard, the role of commensal microbiota in CRC development and response to treatments is emerging as a critical factor. The term microbiome "refers to the microorganisms involved but also encompasses their theatre of activity". In a mutually beneficial and dynamic equilibrium, bacteria coexist on our body stimulating the basal production of tissue repair factors while immune system surveils on pathogens outgrowth. The gut microbiota has been consistently shown to play a role in the development of CRC, The present project will establish the foundation of methods for early detection of the microbiome-immune-induced mutator phenotypes involved in the relapse. Results from this study will pave the way for future interventions to constrain the mutation rates of tumor. Through this prospective observational Microbiome Immune-system Tumor Interaction in Colorectal Oncology (MITICO) project a new platform will be established integrating patient's clinical and lifestyle information with genomic data from both, CRC and the commensal microbiota, along with profiling of local and systemic immune responses.