Research Papers:

STAT1 deficiency supports PD-1/PD-L1 signaling resulting in dysfunctional TNFα mediated immune responses in a model of NSCLC

Juliane Friedrich, Lisanne Heim, Denis I. Trufa, Horia Sirbu, Ralf J. Rieker, Mircea T. Chiriac and Susetta Finotto _

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Oncotarget. 2018; 9:37157-37172. https://doi.org/10.18632/oncotarget.26441

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Juliane Friedrich1, Lisanne Heim1, Denis I. Trufa2, Horia Sirbu2, Ralf J. Rieker3, Mircea T. Chiriac4 and Susetta Finotto1

1Department of Molecular Pneumology, Friedrich Alexander University Erlangen-Nürnberg, Erlangen, Germany

2Department of Thoracic Surgery, Friedrich Alexander University Erlangen-Nürnberg, Erlangen, Germany

3Institute of Pathology, Friedrich Alexander University Erlangen-Nürnberg, Erlangen, Germany

4Department of Medicine 1-Gastroenterology, Pneumology and Endocrinology, Friedrich Alexander University Erlangen-Nürnberg, Erlangen, Germany

Correspondence to:

Susetta Finotto, email: [email protected]

Keywords: NSCLC, STAT1, PDL1

Received: September 30, 2018     Accepted: November 26, 2018     Published: December 14, 2018


In this study we described that Signal Transducer and Activator of Transcription 1 (STAT1) is a key point regulator of PD-1 in tumour infiltrating lymphocytes and PD-L1 in Tumour associated macrophages (TAM) in NSCLC. In our murine model of adenocarcinoma targeted deletion of Stat1 was found associated with enhanced tumour growth, impaired differentiation into M1-like macrophages from the bone marrow, the accumulation of tumor associated macrophages overexpressing PD-L1 and impaired T cell responses in the tumor microenvironment by affecting TNFα responses.

In our human NSCLC patient cohort we found that loss of isoforms STAT1 α and STAT1β mRNA in the tumoural region of the lung correlates with increased tumor size in NSCLC patients. Therefore, STAT1 isoform regulation could be considered for future therapeutical strategies associated to current immune-checkpoint blockade therapy in NSCLC.

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PII: 26441