Group Geisberger

Working Group:
Tumor immunology

Group leader: Dr. Roland Geisberger

Immune cells not only protect us from invading bacterial and viral pathogens, but also combat tranformed malignant cancer cells. The subject of our tumor-immunology research is to decipher the mechanisms by which cancer cells succeed in circumventing clearance by the immune system or even exploit immune cells for tumor growth. In this context, CLL induces an exhausted T cell phenotype marked by Programmed Death 1 (PD!) expression in patients and in the Tcl1 mouse model, which is in the center of our research. Another focus of our group is the quest for the origin of malignant cells and the nature of the mutations underlying malignant transformation and clonal evolution of tumor cells. In this context, we are especially interested in APOBECs, a group of DNA-deaminating enzymes. APOBECs play a crucial role in the immune system but increasing evidence shows that they are also implicated in lymphomagenesis and clonal cancer evolution due to their DNA-damaging activity.

+ Antigen-presenting cells are able to internalize cancer cells, and to present parts of these cells on the cell surface. If these parts are recognized by naive T cells as “dangerous”, they mature into activated effector T cells which can eliminate all cancer cells. Expression of the molecule PD-L1 on the surface of cancer cells protects these cells from a T cell attack. A therapeutic intervention, for example, by a PD-L1 specific antibody makes the cancer cells again vulnerable to an immune attack and leads to a reduction in cancer cells.

Projects

The LIMCR/SCRI is supported by a grant from Gilead Sciences GesmbH entitled “Inferring HLA-haplotypes from existing whole exome and RNA-sequencing datasets to predict neoantigen presentation and anti-CLL immunity”

Grant ID number 06813
Juli 2019

2015

Gold medal for scientific publications, Scientific Award PMU Salzburg, 2015

Dr. Stefan Rebhandl
Research Group: Geisberger

Silver medal for scientific publications, Scientific Award PMU Salzburg, 2015

Michael Huemer, MSc
Research Group: Geisberger

2013

Sanofi Award, 2013

Dr. Nathalie Wacht
Research Group: Geisberger

2018

Exome sequencing of the TCL1 mouse model for CLL reveals genetic heterogeneity and dynamics during disease development.

Zaborsky, N, Gassner, FJ, Höpner, JP, Schubert, M, Hebenstreit, D, Stark, R, Asslaber, D, Steiner, M, Geisberger, R, Greil, R, Egle, A.
Leukemia. 2018.

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Correction to: Fludarabine and rituximab with escalating doses of lenalidomide followed by lenalidomide/rituximab maintenance in previously untreated chronic lymphocytic leukaemia (CLL): the REVLIRIT CLL-5 AGMT phase I/II study.

Egle, A, Steurer, M, Melchardt, T, Weiss, L, Gassner, FJ, Zaborsky, N, Geisberger, R, Catakovic, K, Hartmann, TN, Pleyer, L, Voskova, D, Thaler, J, Lang, A, Girschikofsky, M, Petzer, A, Greil, R.
Ann Hematol. 2018.

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Fludarabine and rituximab with escalating doses of lenalidomide followed by lenalidomide/rituximab maintenance in previously untreated chronic lymphocytic leukaemia (CLL): the REVLIRIT CLL-5 AGMT phase I/II study.

Egle, A, Steurer, M, Melchardt, T, Weiss, L, Gassner, FJ, Zaborsky, N, Geisberger, R, Catakovic, K, Hartman, TN, Pleyer, L, Voskova, D, Thaler, J, Lang, A, Girschikofsky, M, Petzer, A, Greil, R.
Ann Hematol. 2018.

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2017

The Human NADPH Oxidase, Nox4, Regulates Cytoskeletal Organization in Two Cancer Cell Lines, HepG2 and SH-SY5Y.

Auer, S, Rinnerthaler, M, Bischof, J, Streubel, MK, Breitenbach-Koller, H, Geisberger, R, Aigner, E, Cadamuro, J, Richter, K, Sopjani, M, Haschke-Becher, E, Felder, TK, Breitenbach, M.
Front Oncol. 2017, 7:111.

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T cell exhaustion: from pathophysiological basics to tumor immunotherapy.

Catakovic, K, Klieser, E, Neureiter, D, Geisberger, R.
Cell Commun Signal. 2017, 15(1).

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2016

Mesenchymal Stem and Progenitor Cells in Normal and Dysplastic Hematopoiesis -Masters of Survival and Clonality?.

Zaborsky, N, Gassner, FJ, Asslaber, D, Reinthaler, P, Denk, U, Flenady, S, Hofbauer, JP, Danner, B, Rebhandl, S, Harrer, A, Geisberger, R, Greil, R, Egle, A.
Oncotarget. 2016.

CD1d expression on chronic lymphocytic leukemia B cells affects disease progression and induces T cell skewing in CD8 positive and CD4CD8 double negative T cells.

Zaborsky, N, Gassner, FJ, Asslaber, D, Reinthaler, P, Denk, U, Flenady, S, Hofbauer, JP, Danner, B, Rebhandl, S, Harrer, A, Geisberger, R, Greil, R, Egle, A.
Oncotarget. 2016.

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2015

AID/APOBEC deaminases and cancer.

Rebhandl, S, Huemer, M, Greil, R, Geisberger, R.
Oncoscience. 2015, 2(4): 320-333.

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CD4+ T cells, but not non-classical monocytes, are dispensable for the development of chronic lymphocytic leukemia in the TCL1-tg murine model.

Kocher, T, Asslaber, D, Zaborsky, N, Flenady, S, Denk, U, Reinthaler, P, Ablinger, M, Geisberger, R, Bauer, JW, Seiffert, M, Hartmann, TN, Greil, R, Egle, A, Hofbauer, JP.
Leukemia. 2015, xx.

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AIDing cancer treatment: Reducing AID activity via HSP90 inhibition.

Rebhandl, S, Geisberger, R.
Eur J Immunol. 2015, 45(8): 2208-2211.

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Chronic lymphocytic leukaemia induces an exhausted T cell phenotype in the TCL1 transgenic mouse model.

Gassner FJ, Zaborsky N, Catakovic K, Rebhandl S, Huemer M, Egle A, Hartmann TN, Greil R, Geisberger R.
Br J Haematol. 2015 Aug,170(4):515-22. doi: 10.1111/bjh.13467. Epub 2015 May 4.

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AID/APOBEC deaminases and cancer.

Rebhandl S, Huemer M, Greil R, Geisberger R.
Oncoscience. 2015 Apr 28,2(4):320-33. eCollection 2015. Review.

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2014

Chemotherapy-induced augmentation of T cells expressing inhibitory receptors is reversed by treatment with lenalidomide in chronic lymphocytic leukemia.

Gassner FJ, Zaborsky N, Neureiter D, Huemer M, Melchardt T, Egle A, Rebhandl S, Catakovic K, Hartmann TN, Greil R, Geisberger R.
Haematologica. 2014 May,99(5):67-9. doi: 10.3324/haematol.2013.098459. Epub 2014 Feb 21.

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AID induces intraclonal diversity and genomic damage in CD86(+) chronic lymphocytic leukemia cells.

Huemer M, Rebhandl S, Zaborsky N, Gassner FJ, Hainzl S, Weiss L, Hebenstreit D, Greil R, Geisberger R.
Eur J Immunol. 2014 Dec,44(12):3747-57. doi: 10.1002/eji.201344421. Epub 2014 Oct 18.

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APOBEC3 signature mutations in chronic lymphocytic leukemia.

Rebhandl S, Huemer M, Gassner FJ, Zaborsky N, Hebenstreit D, Catakovic K, Grössinger EM, Greil R, Geisberger R.
Leukemia. 2014 Sep,28(9):1929-32. doi: 10.1038/leu.2014.160. Epub 2014 May 20.

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Alternative splice variants of AID are not stoichiometrically present at the protein level in chronic lymphocytic leukemia.

Rebhandl S, Huemer M, Zaborsky N, Gassner FJ, Catakovic K, Felder TK, Greil R, Geisberger R.
Eur J Immunol. 2014 Jul,44(7):2175-87. doi: 10.1002/eji.201343853. Epub 2014 Apr 15.

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2013

Lenalidomide/Rituximab Maintenance After Induction With Fludarabine/Rituximab In Combination With Escalating Doses Of Lenalidomide In Previously Untreated Chronic Lymphocytic Leukemia (CLL): The Revlirit CLL5 AGMT Phase I/II Study, Final Results

Vornamen sind ausgeschrieben-ändern? Alexander Egle, Michael Steurer, Franz Josef Gassner, Roland Geisberger, Thomas Melchardt, Lisa Pleyer, Lukas Weiss, Michael A. Fridrik, Josef Thaler, Alois Lang, Richard Greil,
Blood (ASH Annual Meeting Abstracts). 2013. #4164:

A modified Phenol-chloroform extraction method for isolating circulating cell free DNA of tumor patients.

Hufnagl C, Stöcher M, Moik M, Geisberger R, Greil R.
Journal of Nucleic Acids Investigation. 2013. DOI: 10.4081/jnai.2013.e1

2012

Lysine residue at position 22 of the AID protein regulates its class switch activity.

Geisberger R, Huemer M, Gassner FJ, Zaborsky N, Egle A, Greil R.
PLoS One. 2012,7(2):e30667. doi: 10.1371/journal.pone.0030667. Epub 2012 Feb 20.

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2011

Fludarabine modulates composition and function of the T cell pool in patients with chronic lymphocytic leukaemia.

Gassner FJ, Weiss L, Geisberger R, Hofbauer JP, Egle A, Hartmann TN, Greil R, Tinhofer I.
Cancer Immunol Immunother. 2011 Jan,60(1):75-85. doi: 10.1007/s00262-010-0920-3. Epub 2010 Sep 21.

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A Combination of Fludarabine/Rituximab with Escalating Doses of Lenalidomide in Previously Untreated Chronic Lymphocytic Leukemia (CLL): The REVLIRIT CLL5 AGMT Phase I/II Study, Clinical and Exploratory Analyses of Induction Results

Egle, A, Steurer, M, Gassner, F, Geisberger, R, Melchardt, T, Weiss, L, Fridrik, MA, Thaler, J, Lang, A, Greil, R
BLOOD. 2011, 118(21): 135-136.

“Leukemic cells benefit from deactivating other immune cells. We study the underlying mechanisms and search for ways to reactivate the immune system to combat leukemia.”

Team

Dr. Roland Geisberger
(Supervisor)

Dr. Franz Gassner
(Post-Doc)

Dr. Nathalie Wacht
(Post-Doc)

Kemal Catakovic, MSc
(PhD Student)

Maria Schubert, MSc
(PhD Student)

Stefanie Rauscher, MSc

(PhD Student)

Former Staff:

Dr. Michael Huemer

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