Abteilung für Molekulare Pneumologie

Leitung

Prof. Dr.Dr.Ph.D. Susetta Neurath-Finotto

Überblick Forschungsinhalte

The recognition and elimination of tumor cells by the immune system requires cytotoxic effector functions that are mediated by CD4+ Th1 cells and CD8+ cytotoxic T cells (CTLs), which are inhibited in lung cancer patients. Aim of our group is to set up new immunotherapies to further improve the current effects of the immune checkpoint receptor inhibitors like anti-PD-1 (programmed cell death protein 1) antibodies. PD-1 desensitizes T cell receptor (TCR)-mediated signals and contributes to T cell exhaustion, a state of T cell dysfunction promoting tumour cell growth. In addition, clinical responses to current immunotherapy vary considerably and many patients underlining the need to better understand fundamental molecular mechanisms of this pathway and its role in anti-tumoral immunity. Moreover, a preventive anti-cancer intervention through regulation of the nutrition of the patients with lung cancer is gaining much attention. We recently demonstrated that reducing dietary carbohydrate intake might affect tumor growth and improve current immunotherapy, and target tumor immune escape caused by glucose levels in the tumor microenvironment.

Laufende Forschungsprojekte

• The role of the Transcription factor PU1 in NSCLC (DFG Grant)
• Role of IL-2/IL-2 receptor in NSCLC (Sander Stiftung Grant)
• Role of Blimp-1 in NSCLC
• The role of Glucose in the immunoresponse to NSCLC
• The role of lipids in NSCLC
• The immunoregulation of Fiber rich microenvironmentin NSCLC.

Studien

Development of new immunotherapy for Non-small Cell Lung cancer

Methoden

• Andreev, K., Graser, A., Maier, A., Mousset, S. & Finotto, S. Therapeutical measures to control airway tolerance in asthma and lung cancer. Front Immunol3, 216, doi:10.3389/fimmu.2012.00216 (2012).
• Maxeiner, J. H. et al.A method to enable the investigation of murine bronchial immune cells, their cytokines and mediators. Nat Protoc2, 105-112, doi:10.1038/nprot.2007.8 (2007).
• Sauer, K. A., Scholtes, P., Karwot, R. & Finotto, S. Isolation of CD4+ T cells from murine lungs: a method to analyze ongoing immune responses in the lung. Nat Protoc1, 2870-2875, doi:10.1038/nprot.2006.435 (2006).
• Belli, M. et al.RBE-LET relationship for the survival of V79 cells irradiated with low energy protons.Int J Radiat Biol55, 93-104, doi:10.1080/09553008914550101 (1989).
• Sarto, F. et al.The micronucleus assay in exfoliated cells of the human buccal mucosa. Mutagenesis2, 11-17, doi:10.1093/mutage/2.1.11 (1987).

Kooperationspartner

• Professor, Dr. Daniel Christ, St Vincent's Clinical School, Faculty of Medicine, UNSW, Sydney.
• Prof. Dr. med. Veronika Sexl, University of Veterinary Medicine, Vienna

FAU-Uniklinikum Erlangen: 

I. Medical Clinic:

• Prof. Dr. med. Markus F. Neurath
• Dr. Dentist Mircea T. Chiriac

Department of Thoracic Surgery: 

• Prof. Dr. med. Horia Sirbu
• Dr. med. Denis Trufa

Institut of Pathology

• Prof. Dr. med. Arndt Hartmann
• PD Dr. med. Carol Geppert
• Prof. Dr. med. Ralf J. Rieker

Publikationen

• Heim, L. et al.IL-9 Producing Tumor-Infiltrating Lymphocytes and Treg Subsets Drive Immune Escape of Tumor Cells in Non-Small Cell Lung Cancer. Front Immunol13, 859738, doi:10.3389/fimmu.2022.859738 (2022).
• Gahler, A. et al.Glucose-Restricted Diet Regulates the Tumor Immune Microenvironment and Prevents Tumor Growth in Lung Adenocarcinoma. Front Oncol12, 873293, doi:10.3389/fonc.2022.873293 (2022).
• Heim, L. et al.Increased expression of the immunosuppressive interleukin-35 in patients with non-small cell lung cancer. Br J Cancer120, 903-912, doi:10.1038/s41416-019-0444-3 (2019).
• Kachler, K., Holzinger, C., Trufa, D. I., Sirbu, H. & Finotto, S. The role of Foxp3 and Tbet co-expressing Treg cells in lung carcinoma. Oncoimmunology7, e1456612, doi:10.1080/2162402X.2018.1456612 (2018).
• Heim, L. et al.NFATc1 Promotes Antitumoral Effector Functions and Memory CD8(+) T-cell Differentiation during Non-Small Cell Lung Cancer Development. Cancer Res78, 3619-3633, doi:10.1158/0008-5472.CAN-17-3297 (2018).
• Friedrich, J. et al.STAT1 deficiency supports PD-1/PD-L1 signaling resulting in dysfunctional TNFalpha mediated immune responses in a model of NSCLC. Oncotarget9, 37157-37172, doi:10.18632/oncotarget.26441 (2018).
• Vahl, J. M. et al.Interleukin-10-regulated tumour tolerance in non-small cell lung cancer. Br J Cancer117, 1644-1655, doi:10.1038/bjc.2017.336 (2017).
• Kachler, K. et al.Enhanced Acid Sphingomyelinase Activity Drives Immune Evasion and Tumor Growth in Non-Small Cell Lung Carcinoma. Cancer Res77, 5963-5976, doi:10.1158/0008-5472.CAN-16-3313 (2017).
• Eisenhut, F. et al.FAM13A is associated with non-small cell lung cancer (NSCLC) progression and controls tumor cell proliferation and survival. Oncoimmunology6, e1256526, doi:10.1080/2162402X.2016.1256526 (2017).
• Andreev, K. et al.Impaired T-bet-pSTAT1alpha and perforin-mediated immune responses in the tumoral region of lung adenocarcinoma. Br J Cancer113, 902-913, doi:10.1038/bjc.2015.255 (2015).
• Reppert, S., Koch, S. & Finotto, S. IL-17A is a central regulator of lung tumor growth. Oncoimmunology1, 783-785, doi:10.4161/onci.19735 (2012).
• Neurath, M. F. & Finotto, S. The emerging role of T cell cytokines in non-small cell lung cancer. Cytokine Growth Factor Rev23, 315-322, doi:10.1016/j.cytogfr.2012.08.009 (2012).
• Reppert, S. et al.A role for T-bet-mediated tumour immune surveillance in anti-IL-17A treatment of lung cancer.Nat Commun2, 600, doi:10.1038/ncomms1609 (2011).
• Neurath, M. F. & Finotto, S. IL-6 signaling in autoimmunity, chronic inflammation and inflammation-associated cancer.Cytokine Growth Factor Rev22, 83-89, doi:10.1016/j.cytogfr.2011.02.003 (2011).
• Maxeiner, J. H. et al.A key regulatory role of the transcription factor NFATc2 in bronchial adenocarcinoma via CD8+ T lymphocytes. Cancer Res69, 3069-3076, doi:10.1158/0008-5472.CAN-08-1678 (2009).
• Sauer, K. A. et al.Immunosurveillance of lung melanoma metastasis in EBI-3-deficient mice mediated by CD8+ T cells. J Immunol181, 6148-6157, doi:10.4049/jimmunol.181.9.6148 (2008).

Kontakt

Department of Molecular Pneumology
Hartmannstrasse 14
91052 Erlangen

Susetta.neurath-finotto(at)uk-erlangen.de

09131 85-35883

Weiterführende Links

https://www.molekulare-pneumologie.uk-erlangen.de

Stand: 03/2023