Research Program Immunology, Infection and Cancer - News & Notices
I2@DKFZ: Data and Technique: Thursday 12.12.24 at 16:00 INF 280 K1/K2
Immunology and Infection@DKFZ Seminar Series
Thursday 12.12.24 at 16:00: Data and Technique Talks, Main Building K1/K2
Julian Beyrle (D191) Mild Acid Elution in a Tip (MAETi) enables MS-based immunopeptidomics from as low as 50,000 cells
Shangqing Yang (D430) Identification of host cell vactors associated with HBV virions and subviral particles
Stay up to date with FSP-D news by following us on X (twitter): @DKFZImmunology
PAST SEMINARS
Niels Halama (D196) Immunotherapy for advanced microsatellite stable colorectal cancer and pancreatic cancer
Kam Shing (D440) Deactivation of innate immune cells amplifies the efficacy of immunotherapy in liver cancer
Indrabahadur Singh (D440): Liver Cancer Growth is VPS72-AURKB Axis Dependent
Jürg Nüesch (D430) Portfolio of Selfpropagating Oncosuppressive Protoparvoviruses: Searching for Optimal Properties of Candidate Strains and Variants.
Marie Szczeponik (D490) PharmacoViroTherapy - Combining Small Molecule Compounds with Oncolytic Measles Virus for treatment of Cancer.
Rafael Carretero Coca (D220): CEACAM6: Learning from clinic to optimize drugs
Tim Waterboer (F020) So, you think you have a biomarker? ;-)
Kathrin Wellach (F130) HPV epitope characterization - Development of a life-cell microscopy-based cytotoxicity assay for low-frequency T cells
Matthias Kloor (F210) Cancer immune prevention in high-risk populations
Veronika Frehtman (F010) Biopharmaceutical Processing & Development Unit - Key Factors for Drug Formulation
Development of a next-generation anti-malaria vaccine candidate
Chun-Shan Liu (F240)
From genotype to phenotype: a novel organoid-based model to understand tumor microenvironment alterations with different co-mutations in Idh1-mutated cholangiocarcinoma
Visualizing fate decisions in vivo by optical epitope barcoding and multiplexed imaging.
Xin Li (F180)
ER-stress triggered ATF6 drives gylcolysis and carcinogenesis through education of an immunosuppressive environment.
Preserving cellular identity: APOBEC2 safeguards cell-fate integrity throughout differentiation.
Marco Binder (F170)
High-resolution kinetic characterization of the RIG-I_signaling pathway and the antiviral response.
TCR-antibody fusion proteins as bispecific agents for NK and T cell-mediated immunotherapy
Richard Harbottle (F160)
From Stem-Cells to T-Cells: DNA NanoVectors an Alternative Non-Integrating DNA Vector Platform for Regenerative Medicine and Immunotherapy
Ingrid Hoffmann (F045): The cell cycle on the crossroad of tumorigenesis and cancer
Timo Bund (F200): Implications of Bovine Meat and Milk FActor Protein Expression on Colorectal Cancer - and Beyond
Susanne Pfrommer & Johannes Morschl (F171) Full Spectrum Flow Cytometry - A Hitchhiker's Guide to Immunophenotyping
Dr. Alice O. Kamphorst, who is an Assistant Professor of Oncological Sciences at the Precision Immunology Institute of the Icahn School of Medicine at Mount Sinai and a member of the Cancer Immunology Research Program at the Tisch Cancer Institute.
Alice obtained her PhD at the Rockefeller University and worked on antigen processing and presentation under the supervision of Dr. Michel Nussenzweig. In her post-doctoral studies, she moved to Emory University where she worked on T cells and PD-1 immunotherapy with Dr. Rafi Ahmed.
Her current research focuses on T cell differentiation with a specific interest in situations of chronic persistent antigen stimulation, such as cancer and chronic infections. Her lab studies the effects of costimulation, inflammation and other factors in the microenvironment on CD8 T cell differentiation, dysfunction and response to immunotherapy, in particular PD-1 targeted therapies.
Deciphering the functions of dendritic cell types and their molecular regulation in antiviral and antitumor immunity.
She has extensive experience in the field of innate immunity and Pattern Recognition Receptor(PRRs) systems. The research of her lab focuses on studying the cGAS-STING signaling pathway in innate DNA sensing with a special emphasis on defining its function in physiological contexts that fall outside its classical, infection-associated realm. She has been the recipient of the German Cancer Prize and the Dr. Josef Steiner Cancer Research Award.
Dr. Andrea Schietinger, Group Leader at the Sloan Kettering Institute in the Memorial Sloan Kettering Cancer Center.
Her lab has extensive experience in studying T-cell responses and how they detect cancer cells over the course of tumor development. A primary focus of her team is on understanding the dynamics of how immune cells become unresponsive to tumors and mechanisms that regulate T-cell differentiation.
Dr. Felix Hartmann, who is currently a Postdoctoral fellow at Stanford University.
We are very happy to inform you that he will join the DKFZ in October as a Junior PI. We would like to use this seminar as an opportunity for the DKFZ fraternity to get to know him and his research and stem potential collaborations.
His research combines novel single-cell and imaging proteomic technologies to study interactions of immune cells with the local environment in human cancer. His recent publication outlined a method to characterize the metabolic regulome of single cells together with their phenotypic identity – scMEP (https://doi.org/10.1038/s41587-020-0651-8)
His team has extensive experience in studying mechanisms of uncontrolled autoimmune and Type-II immune responses. In his talk, he will discuss their work on how chronic innate response due to uncontrolled activation of cytosolic DNA sensor pathways leads to autoimmunity.
Dr. Maike de La Roche, a Group Leader at the CRUK-CI, Uni. of Cambridge.
Her team studies differentiation, migration and function of CD8 T cells during the adaptive anti-tumor response. In her talk, she will provide an overview of the different avenues in her laboratory engaged towards defining the roles of Hedgehog signaling in immune cells which may enable novel therapeutic opportunities.
AWARDS
https://www.sitcancer.org/funding/awards/anniversaryawards/sitc2020/2020teamscience
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
Immunoretreat 2024
Immunoretreat 2023
From 25-27 of September 2023, great talks, posters, chain reaction ..... in a relaxing environment.
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!
GRADUATES AND ALUMNI
Lasse Neukirch defended his PhD thesis entitled "Evaluation of antigen-displaying adeno-associated virus-like particles (AAVLPs) as future candidates for personalized cancer vaccination" on the 17th of June 2021.
In his thesis, L. Neukirch tested a novel vaccination strategy to induce CD8+ T cell responses by displaying antigen peptides on the capsid of adeno-associated virus-like particles (AAVLPs).
Vaccination of mice induced CD8+ T cell responses against the displayed antigen that were long-term protective in a B16F10 melanoma model. Generation of these CD8+ T cell responses was promoted by the presence of T helper epitopes in the AAVLP capsid, indicating a distinct advantage of the AAVLP strategy. Vaccination with neoepitope-displaying particles lead to a reduced tumor growth of B16F10 melanomas, which was not achieved by a corresponding peptide vaccination.
Highlights
- AAVLP vaccines induce long-lasting CD8+ T cell responses against displayed antigens
- CD8+ T cell responses are promoted by T helper epitopes in the AAVLP capsid
- AAVLP-display of neoepitopes reduced tumor growth more efficiently than peptide vaccination
Congratulations on this great work!
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!
LATEST PUBLICATIONS
J.P. Lorenzo, L. Molla, E.M. Amro, I.L. Ibarra, S. Ruf, C. Neber, C. Gkougkousis, J. Ridani, P.G. Subramani, J. Boulais, D. Harjanto, A. Vonica, J.M. Di Noia, C. Dieterich, J.B.Zaugg, F.N. Papavasiliou
APOBEC2 safeguards skeletal muscle cell fate through binding chromatin and regulating transcription of non-muscle genes during myoblast differentiation.
Proceedings of the National Academy of Sciences 2024
R. Pecori, I. Chillón, C. Lo Giudice, A. Arnold, S. Wüst, M. Binder, M. Marcia, E. Picardi and F.N. Papavasiliou
ADAR RNA editing on antisense RNAs results in apparent U-to-C base changes on overlapping sense transcripts.
Front. Cell Dev. Biol., 06 January 2023
https://www.frontiersin.org/articles/10.3389/fcell.2022.1080626/full
R. Pecori , S. Di Giorgio , J.P. Lorenzo and F.N. Papavasiliou
Functions and consequences of AID/APOBEC-mediated DNA and RNA deamination.
Nature Reviews Genetics volume 23, pages 505–518 (2022)
B. Casati, J.P. Verdi, A. Hempelmann, M. Kittel, A.G. Klaebisch, B. Meister, S. Welker, S. Asthana, S. Di Giorgio, P. Boskovic, K.H. Man, M. Schopp, P.A. Ginno, B. Radlwimmer, C.E. Stebbins, T. Miethke, F. N. Papavasiliou & R. Pecori
Rapid, adaptable and sensitive Cas13-based COVID-19 diagnostics using ADESSO.
Nature Communications volume 13, Article number: 3308 (2022)
Gross-Cohen M, Yanku Y, Kessler O, Barash U, Boyango I, Cid-Arregui A, Neufeld G, Ilan N, Vlodavsky I
Heparanase 2 (Hpa2) attenuates tumor growth by inducing Sox2 expression.
Matrix Biology, Volume 99, May 2021, Pages 58-71
https://doi.org/10.1016/j.matbio.2021.05.001
Poorebrahim M, Mohammadkhani, N, Mahmoudi, R, Gohlizadeh, Fakhr, E and Cid-Arregui, A.
TCR-like CARs and TCR-CARs targeting neoepitopes: an emerging potential.
Cancer Gene Ther 28, pages 581–589 (2021),
https://doi.org/10.1038/s41417-021-00307-7
Zeelen, J, van Straaten, M, Verdi, J, Hempelmann, A, Hashemi, H, Perez,K, Jeffrey, PD, Hälg, S, Wiedemar, N, Mäser, P, Papavasiliou, FN, Stebbins CE
Structure of trypanosome coat protein VSGsur and function in suramin resistance
Nature Microbiology volume 6, pages392–400(2021)
Poorebrahim M, Melief J, Pico de Coaña Y, L Wickström S, Cid-Arregui A, Kiessling R.
Counteracting CAR T cell dysfunction
Oncogene 40, 421–435 (2021).
https://doi.org/10.1038/s41388-020-01501-x
Fakhr, E, Modic, Z and Cid-Arregui, A.
Recent developments in immunotherapy of cancers caused by human papillomaviruses.
Immunology 2020.
https://doi.org/10.1111/imm.13285
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