Gergő Szűcs1, 2, Éva Imre3, Márton Szentkereszti4, Gabriella Gálffy1, György Losonczy1 Zsolt István Komlósi2, 3, 1
1Department of Pulmonology, Semmelweis University - Budapest (Hungary); 2Department of Genetics, Cell- and Immunobiology, Semmelweis University – Budapest (Hungary); 3Department of Laboratory Medicine, Semmelweis University - Budapest (Hungary), 4First Dept of Pathology, Semmelweis University - Budapest (Hungary)
Introduction: The non-small cell lung cancer (NSCLC) and type 2 diabetes mellitus are frequent diseases all around the world. Monocytes present antigens via major histocompatibility complex class II (MHC II) on their surfaces. Expression of human leukocyte antigen-DR (HLA-DR) a member of MHC class II on the surface of monocytes is important in the development of the anti-tumor immune response. Decreasing expression of HLA-DR on monocytes is associated with poor prognosis in NSCLC. The increased serum fasting glucose concentration (>7 mmol/L) and diabetes mellitus are independent negative prognostic markers in NSCLC, however the mechanisms by which the abnormality of carbohydrate metabolism aggravate lung cancer have not been fully clarified. Nevertheless, hyperglycemia and insulin resistance are known to induce a reduction in HLA-DR expression (immunoparalysis) in sepsis.
Aims: We aimed to investigate the role of carbohydrate metabolism abnormality in NSCLC-related immunoparalysis.
Method: Thirty three advanced (IIIb-IV) NSCLC patients were included in the study. Monocyte HLA-DR expression was analyzed by flow cytometry, serum glucose and insulin concentrations were measured with routine clinical chemical and immunochemical methods. We estimated the insulin resistance with HOMA-IR 2 (Homeostasis Model Assessment – Insulin Resistance 2) score with an online calculator.
Results: Sixteen patients were insulin resistant (HOMA-IR 2 >2). There was a significant indirect correlation between monocyte HLA-DR expression and both insulin concentration and HOMA-IR 2 score. Our results suggest that insulin resistance may contribute to the unfavorable alteration of antigen presentation capacity, and consequently, an insufficient anti-tumor immune response in NSCLC.
Conclusion: These results suggest that keeping the carbohydrate metabolism in balance should be an important element of NSCLC treatment.
Doctroral School: Molecular Medicine
Program: Basic of Human Molecular Genetics and Genetic Diagnostics
Supervisor: Zsolt István Komlósi
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