4.7 Article

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

Journal

CANCER LETTERS
Volume 499, Issue -, Pages 209-219

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2020.11.029

Keywords

OSCC; Diabetes mellitus; TIL; Metabolism; Prognosis

Categories

Funding

  1. German Research Foundation (DFG), Clinical Research Units, Germany [KFO262]

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In patients with oral squamous cell carcinoma, diabetes mellitus type II is associated with abnormal expression of metabolic markers in tumor samples, increased leukocyte infiltration, and elevated CD3(+) T cell numbers, which are crucial for patient outcome. These findings suggest that metabolic differences between diabetic and non-diabetic patients may impact tumor-infiltrating T cells and thus affect patient prognosis.
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 mm(2) 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.

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