UMMS Affiliation

Department of Radiation Oncology

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Amino Acids, Peptides, and Proteins | Cancer Biology | Endocrine System Diseases | Immunotherapy | Neoplasms | Nutritional and Metabolic Diseases | Oncology


OBJECTIVES: Programmed death-ligand 1 (PD-L1) expression is a biomarker for cancer immunotherapy. Diabetes mellitus type-2 is a comorbid disease associated with adverse outcomes in Non-Small Cell Lung Cancer (NSCLC). We aimed to investigate the differences in PD-L1 expression in diabetics.

METHODS: A matched case-control cohort of surgically-resected NSCLC was assembled from an early multicenter study (PMID: 19152440). PD-L1 immunohistochemistry (Clone 22C3) was graded by a tumor positive score (TPS) system (TPS0: no staining; TPS1: < 1%; TPS2: 1-49%; TPS3: > /=50%). Variables showing significance at univariate survival analysis were fit in a Cox regression survival model.

RESULTS: Diabetics (n=40) and nondiabetics (n=39) showed no differences in age, gender, cancer stage, and follow-up. NSCLCs were more likely PD-L1 positive in diabetics but with tumor positivity < 50% (TPS0: 7.5 vs. 20.5%, TPS1: 35 vs. 25.6%, TPS2: 45 vs.23.1%, TPS3: 12.5 vs. 30.8%, respectively; P < 0.05). In diabetics, squamous cell carcinomas (SCC) and adenocarcinomas were mainly TPS2 (65% vs. 20%) and TPS1 (50% vs. 26%), respectively. Peritumoral inflammation correlated with TPS (r=0.228), a relationship accentuated in diabetics (r=0.377, P < 0.05) but diminished and non-significant in nondiabetics (r=0.136, P > /=0.05). This association was stronger in SCC (r=0.424). Diabetes was associated with increased tumor recurrence (HR: 3.08; 95%CI: 1.027-9.23).

CONCLUSION: Diabetes is associated with an increase in peritumoral inflammation, PD-L1 positivity, and recurrence in NSCLC, more pronounced in SCC, suggesting the possibility of metabolic reprogramming and upregulation of PD-L1 by inducible pathways. reserved.


Diabetes, Immunotherapy, Non-small cell lung cancer (NSCLC), PD-L1, Pembrolizumab

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© 2020 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (

DOI of Published Version



Febres-Aldana CA, Poppiti R, Varlotto JM, Voland R, Zaleski M, Sharzehi S, Rassaei N. Diabetes mellitus type 2 is associated with increased tumor expression of programmed death-ligand 1 (PD-L1) in surgically resected non-small cell lung cancer-A matched case-control study. Cancer Treat Res Commun. 2020 Mar 5;23:100170. doi: 10.1016/j.ctarc.2020.100170. Epub ahead of print. PMID: 32179498. Link to article on publisher's site

Journal/Book/Conference Title

Cancer treatment and research communications

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Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.