Preoperative malnutrition is associated with suppressed intratumoral T cell function and distinct tumor-associated microbiota in colorectal cancer: a prospective pilot study

Introduction: Cancer-related malnutrition significantly reduces therapeutic effectiveness, lowers chemotherapy tolerance, and impairs immunotherapy efficacy. Monitoring nutritional status using tools such as the Malnutrition Universal Screening Tool (MUST) may improve clinical outcomes. Malnutrition also profoundly affects immune system functions and gut microbiota composition. However, the relationship between pre-surgery nutritional status, anti-tumor immunity, and tumor-associated microbiota remains poorly understood. Methods: We prospectively enrolled 43 colorectal cancer (CRC) patients who underwent resection surgery between July 2017 and August 2021 at IRCCS Ca' Granda Ospedale Maggiore Policlinico in Milan. Patients were evaluated for biochemical, anthropometric, and nutritional profiles, as well as intratumoral immune phenotypes and tumor-associated microbiota. Tumor-associated microbiota analysis was performed in a subset of 8 patients (5 malnourished and 3 non-malnourished) for whom mucosal samples were available. Results: Malnutrition was associated with increased tissue-infiltrating neutrophils and altered T cell phenotypes, including reduced expression of effector-associated cytokines in conventional T-helper and iNKT cells. Gut microbiota analysis revealed significant associations between neutrophil lymphocyte ratio (NLR) and the bacterial genera Bacteroides, Prevotella, and Parabacteroides, suggesting a potential role for these microbes in shaping immune responses in malnourished individuals. Discussion: These findings suggest a link between malnutrition, gut microbiota composition, and suppressed anti-tumor immunity in CRC patients.