Paving the Path for Immune Enhancing Nutrition in Colon Cancer: Modulation of Tumor Microenvironment and Optimization of Outcomes and Costs

SIMPLE SUMMARY: Proper management of patients undergoing surgery for colorectal cancer is open to research. Three factors influence the immune response against cancer: the genetic makeup of the host, the somatic profile of cancer cells, and the surrounding environment. Immunonutrition has been suggested to impact tumor microenvironment and improve clinical outcomes in operated patients; however, its effects in vivo are far from being fully elucidated. Comparing immune function related indicators in tumor microenvironment before and after immunonutrient supplementation, we showed a favorable modulation towards an enhanced immune response against cancer. In addition to confirming improved short-term outcomes, we found that overall survival was prolonged in patients receiving immunonutrition. Finally, immunonutrition was proven to be a cost saving intervention. This study supports the rationale for implementing immunonutrition in the routine management of patients undergoing surgery for colorectal cancer. ABSTRACT: Introduction. Published evidence suggests that immunonutrition has the potential to decrease postoperative complications and reduce length of stay in patients undergoing surgery for colorectal cancer. However, only a few studies have analyzed the effects of immunonutrition on tumor microenvironment and evaluated its prognostic impact. Material and methods. This is a single center retrospective study enrolling 50 patients undergoing elective surgery for colorectal cancer managed with immunonutrition and 50 patients managed with standard nutrition for comparison. Tumor microenvironment was analyzed before (on the biopsy at the time of diagnosis) and after (on the matched surgical specimen) administration of immunonutrition. Immune function related indicators, including cytotoxic T-lymphocytes, helper T-cells, antigen presenting cells, natural killer cells, T-exhausted lymphocytes, T-regulatory cells, M1 and M2 tumor associated macrophages and PD-L1 expression were assessed by immunohistochemistry. For both groups, clinicopathological data were collected and a 5-year follow-up was available. Results. We found that immunonutrition significantly activated the T-cell response against cancer, alter tumor microenvironment phenotype towards M2 polarization and inhibits the PD1/PD-L1 axis. A lower rate of postoperative complications and a shorter length of stay (p = 0.04) were observed in the immune nutrition group. Compared to standard nutrition group, patients managed wit immune nutrition showed a higher 5-year overall survival (p = 0.001). Finally, immune nutrition allowed to reduce the hospital care costs. Conclusions. Immunonutrition modulates tumor microenvironment by improving immune function and could prolong survival in patients undergoing elective surgery for colorectal cancer. Further studies are needed to optimize IN protocols and confirm their prognostic impact.