Research Program Immunology and Cancer - News & Notices
Immunology, Infection and Inflammation@DKFZ SEMINAR SERIES
29th Oktober 04:00 p.m. Dr. Christos Kyratsous
Rapid selection, characterization and clinical development of fully-human antibodies against emerging infectious diseases.
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PAST SEMINARS
Kevin Bode: Dectin-1 binding to annexins on apoptotic cells induces peripheral immune tolerance via NADPH oxidase-2
Riccardo Pecori: RNA editing modulates pathways critical to B cell lymphomagenesis
"iReceptor plus: Federated Infrastructure for AIRR-seq Data"
"Using functional genetics to understand immune regulation in cancer"
"Panta rhei: Cellular flows in immune responses, hematopoiesis and leukemia"
AWARDS
https://dgfi.org/dgfi-en/awards/koehler-prize/?noredirect=en_US
The work awarded was presented at the German Cancer Congress (DKK) in February 2020, where the award ceremony took place. (https://twitter.com/Stiftung_IO/status/1230163917961334786?s=20)
More information (in German only) can be found here: https://www.dkfz.de/de/presse/pressemitteilungen/2019/dkfz-pm-19-49c-Preis-fuer-die-Weiterentwicklung-von-zellulaeren-Immuntherapien.php
The price was awarded for Dr. Murugans work on immune responses to Plasmodium falciparum (causative agent of malaria) antigens.
Details can be found under
https://dgfi.org/ausgezeichnet-deutsche-gesellschaft-fuer-immunologie-dgfi-ehrt-herausragende-nachwuchswissenschaftler-2/ (in German only)
and
in Murugan, Buchauer et al., Science Immunology 2018 as well was Scally, Murugan et al., Journal of Experimental Medicine 2018.
More information can be found under https://dgfi.org/ausgezeichnet-deutsche-gesellschaft-fuer-immunologie-dgfi-ehrt-herausragende-nachwuchswissenschaftler-2/ (in German only) and
in Schumacher, Bunse et al., Nature 2014 and Bunse, Pusch, Bunse et al., Nature Medicine 2018.
JOURNAL CLUB CANCER IMMUNOTHERAPY
The weekly Journal Club organized by S. Eichmüller, focuses on "Cancer Immunotherapy" and takes place on Mondays at 9.00 a.m. with participants from different departments and research programs of the DKFZ and NCT.
For more information please visit: https://www.dkfz.de/en/gmp-t-zell-therapie/JC-CanImm.html
SAVE THE DATE
SAVE THE DATE: This year no IMMUNORETREAT at Rothenfels Casle
Next Years IMMUNORETREAT 10 - 12 of May 2021.
Immunoretreat 2019 - Three days of exciting immunology on beautiful Rothenfels Castle
From 13-15 of May 2019, FSD scientists gathered at the Castle of Rothenfels for our annual retreat.
Many thanks to Thorsten Feyerabend for the fantastic organization!
© T. Feyerabend
GRADUATES AND ALUMNI
© dkfz.de
Kevin Bode defended his PhD thesis entitled "Molecular analysis of annexin receptor-induced immunosuppression in autoimmunity and tumor growth" on the 13th of March 2020.
In his thesis and in a paper published in Cell Reports, K.Bode and colleagues identify Dectin-1 on dendritic cells as a novel receptor for apoptotic cell-bound annexins, responsible for induction of peripheral immune tolerance. Tolerogenic signaling depends on selective SYK-phosphorylation and production of reactive oxygen species via NADPH oxidase-2. Dectin-1-deficient mice generate stronger immune responses against apoptotic cells and develop autoimmunity.
Highlights
- Dectin-1 is a tolerogenic receptor for annexins on the surface of apoptotic cells
- Annexin-binding to Dectin-1 induces selective SYK-phosphorylation
- SYK-dependent ROS-production via NOX-2 is critical for tolerogenic signaling
- Dectin-1 deficiency causes autoimmunity
Congratulations Dr. Bode!
FSP-D PhD Graduates - 2019
Thesis Abstract: Our study revealed that SPTLC2 underpins the adaptive protective immunity by translating extracellular stimuli into intracellular anabolic signals and reducing the cellular stress in maintaining metabolic reprogramming sustainability. In addition, SPTLC2 is required to maintain the suppressive activity of Treg cells to keep the immune tolerance and restrict the anti-tumor responses. Collectively, we address that the SPTLC2-mediated sphingolipid de novo synthetic pathway synchronizes metabolic reprogramming and the immune reaction of regulatory and effector T cells in infection and cancer.
Abstract: T cell receptor (TCR) engagement and subsequent signalling are a prerequisite to initiate a T cell immune response. This study examined the role of Thioredoxin-interacting protein (TXNIP) in TCR signalling and shows that TXNIP acts as transcriptional inhibitor. Hence, TXNIP might be considered as a potential therapeutic target to shape T cell responses e.g. in autoimmune or tumour diseases.
Congratulations on this excellent work!
Abstract: My PhD work was focusing on the characteristic frameshift mutations of the Notch1 PEST domain, leading to the expression of a truncated, hyperactive Notch1 protein. These mutations are found with very high frequencies in human T-ALL, and also in our spontaneous T-ALL mouse model. To investigate the importance of such frameshift mutations in leukemia pathogenesis, we developed a modified Notch1 allele, where frameshift mutations are non-functional. Interestingly, mice bearing such a modified Notch1 allele overcome frameshift disability by specifically acquiring direct STOP mutations leading to a truncated PEST domain. Overall, our results reveal an enormous selection pressure for mutations leading to a hyperactive Notch signaling in T-ALL pathogenesis.
Congratulations Dr. Kongsaysak-Lengyel!
Abstract: In my PhD project I investigated the regulation of the hematopoietic system, and in particular HSC, under stress conditions. To enable HSC fate mapping, I employed a Cre knock-in reporter mouse and performed time-resolved analysis of hematopoietic compartment sizes and label propagation. Our findings show that the activation of HSC, in terms of differentiation, depends strongly on the nature of the challenge, giving important insights on the hematopoietic response to severe insults such as sepsis and irradiation.
Congratulations on this great work!
On the 10th of September 2019, Stefanie Dünnbier defended her doctoral thesis entitled "The role of Thioredoxin-interacting protein in T cell receptor signalling".
Abstract: T cell receptor (TCR) engagement and subsequent signalling are a prerequisite to initiate a T cell immune response. This study examined the role of Thioredoxin-interacting protein (TXNIP) in TCR signalling and shows that TXNIP acts as transcriptional inhibitor. Hence, TXNIP might be considered as a potential therapeutic target to shape T cell responses e.g. in autoimmune or tumour diseases.
Congratulations on this excellent work!
On the 10th of Mai 2019, Csilla Kongsaysak-Lengyel defended her PhD. The title of her thesis is "Importance of Notch1 PEST domain mutations in T-cell acute lymphoblastic leukemia".
Abstract: My PhD work was focusing on the characteristic frameshift mutations of the Notch1 PEST domain, leading to the expression of a truncated, hyperactive Notch1 protein. These mutations are found with very high frequencies in human T-ALL, and also in our spontaneous T-ALL mouse model. To investigate the importance of such frameshift mutations in leukemia pathogenesis, we developed a modified Notch1 allele, where frameshift mutations are non-functional. Interestingly, mice bearing such a modified Notch1 allele overcome frameshift disability by specifically acquiring direct STOP mutations leading to a truncated PEST domain. Overall, our results reveal an enormous selection pressure for mutations leading to a hyperactive Notch signaling in T-ALL pathogenesis.
Congratulations Dr. Kongsaysak-Lengyel!
On the 29th of April 2019, Ann-Kathrin Fanti defended her PhD thesis entitled "Fate Mapping of Hematopoietic Stem Cell Activity under Challenges".
Abstract: In my PhD project I investigated the regulation of the hematopoietic system, and in particular HSC, under stress conditions. To enable HSC fate mapping, I employed a Cre knock-in reporter mouse and performed time-resolved analysis of hematopoietic compartment sizes and label propagation. Our findings show that the activation of HSC, in terms of differentiation, depends strongly on the nature of the challenge, giving important insights on the hematopoietic response to severe insults such as sepsis and irradiation.
Congratulations on this great work!
LATEST PUBLICATIONS
Wu J, Weisshaar N, Hotz-Wagenblatt A, Madi A, Ma S, Mieg A, Hering M, Mohr K, Schlimbach T, Borgers H, Cui G.
Skeletal muscle antagonizes antiviral CD8+ T cell exhaustion.
Science Advances (2020) 6:eaba3458
Murugan R, Scally SW, Costa G, Mustafa G, Thai E, Decker T, Bosch A, Prieto K, Levashina EA, Julien J-P & Wardemann H
Evolution of protective human antibodies against Plasmodium falciparum circumsporozoite protein repeat motifs
Nat Med (2020)
Aslan K, Turco V, Blobner J, Sonner JK, Liuzzi AR, Núñez NG, De Feo D, Kickingereder P, Fischer M, Green E, Sadik A, Friedrich M, Sanghvi K, Kilian M, Cichon F, Wolf L, Jähne K, von Landenberg A, Bunse L, Sahm F, Schrimpf D, Meyer J, Alexander A, Brugnara G, Röth R, Pfleiderer K, Niesler B, von Deimling A, Opitz C, Breckwoldt MO, Heiland S, Bendszus M, Wick W, Becher B & Platten M.
Heterogeneity of response to immune checkpoint blockade in hypermutated experimental gliomas
Nat Commun 11, 931 (2020).
Bode K, Bujupi F, Link C, Hein T, Zimmermann S, Peiris D, Jaquet V, Lepenies B, Weyd H and Krammer PH
Dectin-1 binding to annexins on apoptotic cells induces peripheral immune tolerance via NADPH oxidase-2
Cell Reports. Volume 29, Dec 2019, Pages 4435-4446.e9
Calculating germinal centre reactions
Current Opinion in Systems Biology (Dec 2019)
Dorshkind K, Höfer T, Montecino-Rodriguez E, Pioli PD, Rodewald HR
Do haematopoietic stem cells age?
Nature Reviews Immunology (Nov 2019); PMID 31740804