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Tumor-stromal-immune cells crosstalk in cancer

The tumor microenvironment is increasingly recognized as a crucial component of tumorigenesis. The interaction between cancer cells and stromal cells plays a significant role in tumor progression and often determines the response to therapy. Our research aims to understand how the microenvironmental niche drives tumor progression and, more importantly, to identify specific targets that can interact with or inhibit the maintenance and functional competence of the tumor niche. We seek to develop new translational approaches that target different stromal and immune cell populations and their corresponding signaling systems. Our primary focus is on pancreatic cancer, lung cancer, and leukemia. Specifically, we investigate the pathological role of fibroblasts, macrophages, and their cross-talk with cytotoxic immune cells. Our goal is to identify novel molecular targets within the tumor microenvironment that may facilitate the development of effective anti-cancer therapies. Additionally, we employ nanoparticle-mediated methodology to deliver bioactive molecules such as nucleic acids, small molecular drugs, peptides, etc., into immune cells, aiming to enhance the efficacy of anti-cancer therapy. We combine basic research with translational aspects, analyzing liquid and tumor tissue biopsies, and utilizing mouse models of cancer to gain insights into the complex interplay between cancer cells and the microenvironment.

 Highlighted publications

Karimova AF, Ketkar A, Suezov R, Khalitova AR, Gomzikova M, Mukhamedshina Y, Lauth M, Huber M, Simon HU, Brichkina A. In vitro functional assays to assess the reciprocal interplay between tumor cells and macrophages. FASEB J. 2024 Jul 15;38(13):e23730. doi: 10.1096/fj.202400240R. IF 4.7

Brichkina A, Ems M, Suezov R, Singh R, Lutz V, Picard FSR, Nist A, Stiewe T, Graumann J, Daude M, Diederich WE, Finkernagel F, Chung HR, Bartsch DK, Roth K, Keber C, Denkert C, Huber M, Gress TM, Lauth M. DYRK1B blockade promotes tumoricidal macrophage activity in pancreatic cancer. Gut. 2024 Jun 4:gutjnl-2023-331854. doi: 10.1136/gutjnl-2023-331854. IF 24.5

Brichkina A*, Suezov R, Huber M*. Methyltransferase-like 3 (METTL3) inhibition potentiates anti-tumor immunity: a novel strategy for improving anti-PD1 therapy. Signal Transduct Target Ther. 2023 Dec 11;8(1):448. doi: 10.1038/s41392-023-01696-x. IF 39.3

Brichkina A, Polo P, Dharamvir Sharma S, Visestamkul N, Lauth M. A quick guide to CAF subtypes in pancreatic cancer. Cancers. 2023. 15(9). doi: 10.3390/cancers15092614 IF 6.57

Brichkina A*, Simon H-U*. A novel role for mitochondrial fission in macrophages: trained innate immunity induced by beta-glucan. Cell Mol Immunology. 2023 Apr 17 doi: 10.1038/s41423-023-01017-w. IF 20.1

Picard F*, Lutz V*, Brichkina A*, Neuhaus F, Ruckenbrod T, Hupfer A, Raifer H, Klein M, Bopp T, Pfefferle PI, Savai R, Prinz I, Waisman A, Moos S, Chang HD, Heinrich S, Bartsch DK, Buchholz M, Singh S, Tu M, Klein L, Bauer C, Liefke R, Burchert A, Chung HR, Mayer P, Gress TM, Lauth M, Gaida M, Huber M. IL-17A-producing CD8+ T cells promote PDAC via induction of inflammatory cancer-associated fibroblasts. Gut. 2023 Feb 9:gutjnl-2022-327855. IF 31.8

Enukashvily NI, Ponomartsev NV, Ketkar A, Suezov R, Chubar AV, Prjibelski AD, Shafranskaya DD, Elmshäuser S, Keber CU, Stefanova VN, Akopov AL, Klingmüller U, Pfefferle PI, Stiewe T, Lauth M, Brichkina A. Pericentromeric satellite lncRNAs are induced in cancer-associated fibroblasts and regulate their functions in lung tumorigenesis. Cell Death Dis. 2023 Jan 12;14(1):19. IF 9.68

Novoselova M, Loh HM, Trushina D, Ketkar A, Abakumova T, Zatsepin T, Kakran M, Brzozowska A, Hong LH, Gorin D, Antipina M, Brichkina A. Biodegradable Polymeric Multilayer Capsules for Therapy of Lung Cancer. ACS Applied Materials and Interfaces 12, 5610-5623, 2020.  IF 10.38

Brichkina A and Bulavin DV. Cancer suppression by systemic inactivation of p38MAPK. Oncotarget Feb 11, doi: 10.18632/oncotarget.15293, 2017. IF 5.31

Brichkina A, Bertero T, Loh HM, Nguyen NTM, Emelyanov A, Rigade S, Ilie M, Hofman P, Gaggioli C, Bulavin DV. p38MAPK builds a hyaluronan cancer niche to drive lung tumorigenesis. Genes Dev 30, 2623–2636, 2016. IF 13.62

Brichkina A, Nguyen NT, Baskar R, Wee S, Gunaratne J, Robinson RC, Bulavin DV. Proline isomerisation as a novel regulatory mechanism for p38MAPK activation and functions. Cell Death Differ 23, 1592-601, 2016. IF 12.89

Le Guezennec X, Brichkina A, Huang YF, Kostromina E, Han W, Bulavin DV. Wip1-dependent regulation of autophagy, obesity, and atherosclerosis. Cell Metabolism 16, 68-80, 2012. IF 35.1

Brichkina A and Bulavin D. Wip-ing out atherosclerosis with autophagy. Autophagy 8, 1545-17, 2012. IF 16.14

Funding

DFG BR 5849/1-1, KFO325 start-up, UKGM (2/2019 MR), Novartis-Stiftung, Deutsche Jose Carreras Leukemia Stiftung (14 R/2020 and 19 R/2023), Anneliese Pohl Habilitationsförderung

Group members

Roman Suezov, PhD student
Ibrahim Gouda, Master student
Karina Goncharova, Bachelor student
Susana Santos Batista, Bachelor student

Alumni

Simon Molitor, MD student (2022)
Avanee Ketkar, PhD student (2018-2022)
Adelya Mullakhmetova, exchanged PhD student (Kazan Federal University, Russia; 2021)
Stanislav Perevoschykov, exchanged PhD student (DAAD-GRISC fellowship L-2021-4_d, Skolkovo Institute of Science and Technology; 2021)
Anna Chubar, exchanged PhD student (DAAD-GRISC fellowship L-2020a-2_d, Institute of Cytology, Saint-Petersburg, Russia; 2020)

We are looking for motivated undergraduate students aiming to perform Bachelor, Master or MD thesis or gain practical experience.
If you are interested – please feel free to contact us via email anna.brichkina@staff.uni-marburg.de

Contact

Anna Brichkina
Zentrum für Tumor- und Immunbiologie
Hans-Meerwein-Straße 3
Room 03/0120

Tel. 06421-28 25388
Email: anna.brichkina@staff.uni-marburg.de