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

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.

• Authors: Gerrit Spanier, Ines Ugele, Felix Nieberle, Luisa Symeou, Sandra Schmidhofer, Almut Brand, Johannes Meier, Steffen Spoerl, Rosemarie Krupar, Petra Rümmele, Peter Siska, Kathrin Renner, Katrin Peter, Michael Gerken, Philipp Beckhove, Torsten E Reichert, Marina Kreutz, Katrin Singer
• Journal: Cancer letters (Cancer Lett) Vol. 499 Pg. 209-219 (02 28 2021) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 33276040 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.

Chemical References

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

Topics

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