The Negative Impact of Body Mass Index on the Tumor Microenvironment in Colon Cancer: Results of a Prospective Trial

Ann Surg Oncol. 2018 May;25(5):1374-1380. doi: 10.1245/s10434-018-6405-x. Epub 2018 Mar 12.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Clinical Trial

MeSH terms

  • Aged
  • Body Mass Index*
  • CD3 Complex / metabolism
  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes / metabolism
  • Colonic Neoplasms / immunology*
  • Colonic Neoplasms / metabolism*
  • DNA Mismatch Repair*
  • DNA-Binding Proteins / metabolism
  • Disease-Free Survival
  • Female
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Lymphatic Metastasis
  • Lymphocyte Count
  • Male
  • Mismatch Repair Endonuclease PMS2 / metabolism
  • MutL Protein Homolog 1 / metabolism
  • MutS Homolog 2 Protein / metabolism
  • Obesity / genetics
  • Obesity / immunology*
  • Prospective Studies
  • Random Allocation
  • Tumor Microenvironment / immunology*

Substances

  • CD3 Complex
  • DNA-Binding Proteins
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • G-T mismatch-binding protein
  • MLH1 protein, human
  • PMS2 protein, human
  • MSH2 protein, human
  • Mismatch Repair Endonuclease PMS2
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein