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| Angebotsdatum: |
27. April 2022
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| Art der Stelle: |
Doktorarbeit |
| Fachgebiet: |
Humanmedizin > Innere Medizin
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| Titel des Themas: |
Analysis of the immune checkpoint function of TAM receptors in anti-tumor NK cell responses
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| Institut: |
Universitätsmedizin Mannheim, Abteilung Personalisierte Onkologie mit Schwerpunkt Lungenkarzinom
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| Adresse: |
| Frau Victoria Gensch |
| Im Neuenheimer Feld 280 |
| 69120 Heidelberg |
| Tel.: Fax.:
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| Bundesland: |
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| Homepage: |
http://https://www.umm.uni-heidelberg.de/grk2727/
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| E-Mail Kontakt: |
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| Beschreibung: |
The introduction of immune checkpoint inhibitors has revolutionized treatment of cancer patients. However, only approximately 20% of patients show long-term benefit. Therefore, additional strategies are needed to improve the overall efficacy of cancer immune therapy. In this context, NK cells are of special interest because they can directly kill cancer cells. Previous data show that the tumor associated macrophage receptors (TAMR) expressed on NK cells, function as negative immune checkpoints as their simultaneous inhibition can lead to improved tumor cell killing by NK cells. We hypothesize that targeting one TAM-receptor is sufficient to enhance the anti-tumor effector functions of NK cells and propose to dissect the unknown functions of each individual TAMR. The MD student will investigate the translational relevance of this approach by determining TAMR expression by circulating and tumor-infiltrating NK cells in cancer patients.
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| Methoden: |
Sample procession (blood biopsies), MACS, RT qPCR, FACS, statistical anaysis
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| Anfangsdatum: |
1. August 2022 |
| Geschätzte Dauer: |
12 Monate
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| Bezahlung: |
Ja
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| Papers: |
1. Bauer R, Udonta F, Wroblewski M, Ben-Batalla I, Santos IM, Taverna F, Kuhlencord M, Gensch V, Päsler S, Vinckier S, Brandner JM, Pantel K, Bokemeyer C, Vogl T, Roth J, Carmeliet P, Loges S. 2018. Blockade of Myeloid-Derived Suppressor Cell Expansion with All-Trans Retinoic Acid Increases the Efficacy of Antiangiogenic Therapy. Cancer Research 78: 3220-3232.
2. Wroblewski M, Bauer R, Cubas Córdova M, Udonta F, Ben-Batalla I, Legler K, Hauser C, Egberts J, Janning M, Velthaus J, Schulze C, Pantel K, Bokemeyer C, Loges S. 2017. Mast cells decrease efficacy of anti-angiogenic therapy by secreting matrix-degrading granzyme B. Nature Communications 8(1): 269.
3. Ben-Batalla I, Erdmann R, Jørgensen H, Mitchell R, Ernst T, von Amsberg G, Schafhausen P, Velthaus JL, Rankin S, Clark RE, Koschmieder S, Schultze A, Mitra S, Vandenberghe P, Brümmendorf TH, Carmeliet P, Hochhaus A, Pantel K, Bokemeyer C, Helgason GV, Holyoake TL, Loges S. 2017. Axl Blockade by BGB324 inhibits BCR-ABL tyrosine kinase inhibitor-sensitive and -resistant Chronic Myeloid Leukemia. Clinical Cancer Research 23: 2289-2300.
4. Waizenegger JS, Ben-Batalla I, Weinhold N, Meissner T, Wroblewski M, Janning M, Riecken K, Binder M, Atanackovic D, Taipaleenmaeki H, Schewe D, Sawall S, Gensch V, Cubas-Cordova M, Seckinger A, Fiedler W, Hesse E, Kröger N, Fehse B, Hose D, Klein B, Raab MS, Pantel K, Bokemeyer C, Loges S. 2015. Role of Growth arrest-specific gene 6-Mer axis in multiple myeloma. Leukemia 29(3):696-704.
5. Ben-Batalla I, Schultze A, Wroblewski M, Erdmann R, Heuser M, Waizenegger JS, Riecken K, Binder M, Schewe D, Sawall S, Witzke V, Cubas-Cordova M, Janning M, Wellbrock J, Fehse B, Hagel C, Krauter J, Ganser A, Lorens JB, Fiedler W, Carmeliet P, Pantel K, Bokemeyer C, Loges S. 2013. Axl, a prognostic and therapeutic target in acute myeloid leukemia mediates paracrine crosstalk of leukemia cells with bone marrow stroma. Blood 122: 2443-2452.
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| Sonstiges: |
Regelmäßige Seminare, Journal Clubs und Retreats, enge Zusammenarbeit mit DKFZ Abteilung
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