The Negative Impact of Body Mass Index on the Tumor Microenvironment in Colon Cancer: Results of a Prospective Trial
The association between tumor mismatch repair status and obesity in colon cancer is not well understood. The authors of this study hypothesized that mismatch repair deficiency in colon cancer may be associated with a lower Body Mass Index (BMI) and improved patient outcome due to an enhanced tumor immune microenvironment.
For this study, 70 patients were randomly selected from a prospective trial evaluating nodal ultrastaging for colon cancer. The mismatch repair status of tumors and immunomarker expression were correlated with clinicopathologic characteristics and evaluated for disease-free survival.
Patients with mismatch repair-deficient tumors (n = 11) had a lower mean BMI than those with mismatch repair-proficient tumors (n = 59) (22.16 vs. 26.30 kg/m2, respectively; p = 0.029).The findings showed that CD3+ T cells were inversely associated with mismatch repair proficiency (p = 0.048). Mismatch repair-proficient tumors in nonobese patients (BMI < 30 kg/m2) versus obese patients had a higher density of CD8+ (p = 0.008) and FOXP3+ (p = 0.005) T cells. Multivariable analysis linked CD4+ (hazard ratio [HR] 0.52; 95% confidence interval [CI] 0.35–0.76), CD8+ (HR 0.67; 95% CI 0.50–0.89), and number of tumor-positive lymph nodes (HR 1.19; 95% CI 1.03–1.36) to disease-free survival for patients with mismatch repair-proficient tumors.
Tumor mismatch repair status and obesity are correlated in patients with colon cancer. Increased intratumoral T cells in nonobese patients suggests an unexplored link between tumor mismatch repair and immunoprofile.
Financial support for the NYULMC Experimental Pathology Immunohistochemistry Core Laboratory and Clarient Diagnostic Services was provided in part by the Laura and Isaac Perlmutter Cancer Center Support grant NIH/NCI P30CA016087 and the National Institutes of Health Shared Instrumentation (S10) Grants NIC/ORIP S10OD0D10584-01A1 and S10ODOD10584-01A1. Author D.C.F is currently with Valley Health Surgical Oncology, Winchester, VA. Author D.J.L. is currently the Director of the Dermatological Center for Skin Health at Providence Saint John’s Health Center and the Division Chief Dermatology and Residency Program Director at Harbor-UCLA Medical Center, Torrance, California. This project was support by funds from the National Cancer Institute (RO1CA090848) and the California Oncology Research Institute. The authors take sole responsibility for the data reported, and the content within the manuscript in no way represents official views of the National Cancer Institute or the National Institutes of Health.
- 1.World Health Organization. Obesity and overweight. http://www.who.int/mediacentre/factsheets/fs311/en/ (2018). Accessed 14 Jan 2018.
- 7.Booth A, Magnuson A, Fouts J, Foster M. Adipose tissue, obesity, and adipokines: role in cancer promotion. Horm Mol Biol Clin Invest. 2015;21:57–74.Google Scholar