The predictive power of CD3+ T cell infiltration of oral squamous cell tumors is limited to non-diabetic patients

Cancer Lett. 2021 Feb 28:499:209-219. doi: 10.1016/j.canlet.2020.11.029. Epub 2020 Dec 1.

Abstract

Diabetes mellitus type II (DM) and immune cell infiltration determine patient outcome in many tumor entities. Here we studied a possible link between the metabolic and immune cell status of OSCC patients. Glucose transporter (GLUT) 1 mRNA expression was elevated in all tumor samples, whereas other glycolytic markers such as lactate dehydrogenase (LDH) A or monocarboxylate transporter (MCT) 1 were increased in tumor samples from patients with diabetes and these patients had a significantly worse prognosis compared to non-diabetic patients. Analyses of immune cell infiltration in tumors from diabetic and non-diabetic patients revealed an increased leukocyte (CD45+) infiltration compared to normal mucosa only in non-diabetic patients. In line, the amount of CD3+ T cells per mm2 tumor tissue, was elevated in patients without diabetes and crucial for patient outcome in OSCC patients without diabetes, as compared to healthy mucosa using fluorescence immunohistochemistry in tissue microarrays of 229 patients. Our results demonstrate that diabetes is a prognostic factor for OSCC patients and associates with decreased leukocyte and CD3+ infiltration indicating that metabolic differences between diabetic and non-diabetic patients may alter tumor-infiltrating T cells and thereby determine patient outcome.

Keywords: Diabetes mellitus; Metabolism; OSCC; Prognosis; TIL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD3 Complex / metabolism
  • Diabetes Mellitus, Type 2 / epidemiology*
  • Diabetes Mellitus, Type 2 / immunology
  • Diabetes Mellitus, Type 2 / metabolism
  • Glucose Transporter Type 1 / metabolism
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Male
  • Middle Aged
  • Monocarboxylic Acid Transporters / metabolism
  • Mouth Mucosa / immunology
  • Mouth Mucosa / pathology
  • Mouth Mucosa / surgery
  • Mouth Neoplasms / immunology
  • Mouth Neoplasms / metabolism
  • Mouth Neoplasms / mortality*
  • Mouth Neoplasms / surgery
  • Predictive Value of Tests
  • Prognosis
  • Risk Assessment / methods
  • Risk Assessment / statistics & numerical data
  • Risk Factors
  • Squamous Cell Carcinoma of Head and Neck / immunology
  • Squamous Cell Carcinoma of Head and Neck / metabolism
  • Squamous Cell Carcinoma of Head and Neck / mortality*
  • Squamous Cell Carcinoma of Head and Neck / surgery
  • Symporters / metabolism
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Warburg Effect, Oncologic

Substances

  • CD3 Complex
  • Glucose Transporter Type 1
  • Monocarboxylic Acid Transporters
  • SLC2A1 protein, human
  • Symporters
  • monocarboxylate transport protein 1