Innate Immunity Research Group
Our group investigates the role of a newly discovered group of immune cells termed innate lymphoid cells (ILCs) within the tumor microenvironment and their interactions with malignant and non-malignant stromal cells, using a variety of interdisciplinary approaches. Our long-term research objective is to increase our understanding of the mechanisms of tumor development and identify novel diagnostic and prognostic biomarkers as well as prospective therapeutic targets.
Cancer is a major public health concern worldwide. Among the most common types of cancer are those, which manifest themselves at barrier tissues, including the skin, lung and intestine. Recently, a novel group of immune cells residing primarily at such barrier tissues was discovered and named innate lymphoid cells (ILCs).
ILCs are lymphocytes, which, unlike T and B cells, lack the expression of somatically rearranged antigen receptors and surface markers that identify their immune cell ancestry. Based on the type of cytokines produced and the transcription factors expressed, ILCs have been subdivided into five distinct subsets: natural killer (NK) cells, group 1 innate lymphoid cells (ILC1s), ILC2s, ILC3s and lymphoid tissue inducer (LTi) cells.
The major task of ILCs is the maintenance of tissue homeostasis. However, the role of ILCs in cancer seems contradictory as they have been separately associated with tumor-promoting as well as tumor-suppressing activities.
A major current goal of our research is to understand the difference between protective and pathogenic function of ILCs. In particular, we work under the assumption that the role of ILCs in cancer is defined by the type of interactions with molecular and cellular components of the tumor microenvironment.
ILC2s make up the primary ILC population in the skin. Using melanoma, the most malignant form of skin cancer as a model, we have found that they exert an anti-tumor response through the recruitment and activation of eosinophils. In contrast, melanoma cells deploy an array of mechanisms such as an acidification of the tumor microenvironment, in order to escape recognition and destruction by ILC2s (Wagner and Koyasu, 2019 Trends Immunol; Wagner et al., 2020 Cell Reports).
Insights into how different tumor microenvironments and their cellular and non-cellular components affect ILCs offer an opportunity to increase our understanding of the mechanisms of tumor development and identify novel diagnostic and prognostic biomarkers as well as prospective therapeutic targets.
Marek Wagner received his PhD in cancer research from the University of Bergen (Bergen, Norway) with part of his research performed at Harvard Medical School & Children’s Hospital Boston (Boston, USA) as a member of the Vascular Biology Program established by Dr. Judah Folkman. For his doctoral studies, he focused on the tumor microenvironment and made a seminal discovery by identifying an angiogenic potential of tumor-associated adipose tissue (Wagner et al., Angiogenesis 2012). During his postdoctoral training at the University of Bergen (Bergen, Norway), he found that the establishment of the tumor inflammatory microenvironment depends on the presence of functional lymphatic vessels (Lund and Wagner et al., JCI 2016). He also joined RIKEN (Yokohama, Japan) and worked in the laboratory headed by Dr. Shigeo Koyasu who identified a subset of innate lymphocytes, which produce type 2 cytokines and are now called group 2 innate lymphoid cells (ILC2s). Together with Dr. Koyasu, he contributed to the development of a new field of immunology by carrying out studies to assess the role of ILC2s in the tumor growth and progression (Wagner et al., Cell Reports 2020). From January 2023, Marek is leading the Innate Immunity Research Group at Łukasiewicz – PORT (Wrocław, Poland).
If you are interested in joining our group, contact us at:
marek.wagner@port.lukasiewicz.gov.pl
Ela holds an MSc degree in Biology from the University of Wrocław. She acquired laboratory experience as a diagnostician at a veterinary laboratory and furthered her expertise at the University of Wrocław, where she served as a laboratory technician at the Department of Molecular Cell Biology. In our team, Ela serves as a laboratory manager, offering support to members in their daily tasks. She is responsible for budget control, orders, documentation, and overall lab organization.
Martyna earned her PhD degree in cancer immunology at the Ludwik Hirszfeld Institute of Immunology and Experimental Therapy PAS. Her research focused on investigating the role of tumor-associated macrophages (TAMs) in breast cancer within the context of vitamin D influence on the tumor microenvironment. During her study, she characterized TAMs in the context of metastatic phenotype and explored the ability of monocytes and bone marrow progenitors to polarize towards pro- or anticancer macrophages, all correlated with the vitamin D status and stage of the disease in mice/patients. She also completed a short-term internship at the State University of New York during her academic journey. In our team, as a post-doc, she is dedicated to identifying novel activators of ILC2s in melanoma, continuing her research interests related to vitamin D.
Mateusz holds an MSc degree in Biotechnology from the Wrocław University of Science and Technology. His expertise lies at the intersection of molecular biology, microbiology and pharmacy. He also holds postgraduate qualifications in Quality Management. Throughout his career, he has served as a microbiologist in both manufacturing and service sectors. Initially joining our team as a laboratory manager, he is currently pursuing doctoral studies at the Medical University of Wrocław with a focus on cancer immunology. In the course of his research, he aims to dissect the interplay between innate immune cells and stromal cells within the tumor microenvironment of melanoma.
2023
- Innate lymphoid cells and tumor-derived lactic acid: novel contenders in an enduring game.
Marciniak M, Wagner M. Front Immunol. PMID: 37868977
2022
- Cancer immunosurveillance by ILC2s.
Wagner M, Koyasu S. Trends Cancer. PMID: 35871054 - ILC2s and Adipose Tissue Homeostasis: Progress to Date and the Road Ahead.
Misawa T, Wagner M, Koyasu S. Front Immunol. PMID: 35784368
2021
- Pharmacokinetics and Pharmacodynamics of T-Cell Bispecifics in the Tumour Interstitial Fluid.
Eigenmann MJ, Karlsen TV, Wagner M, Tenstad O, Weinzierl T, Fauti T, Grimm HP, Skogstrand T, Klein C, Sam J, Umana P, Bacac M, Wiig H, Walz AC. 2021. PMID: 34959386 - Innate Lymphoid Cells in Skin Homeostasis and Malignancy.
Wagner M, Koyasu S. Front Immunol. PMID: 34691082
2020
- A 3D Skin Melanoma Spheroid-Based Model to Assess Tumor-Immune Cell Interactions.
Wagner M, Koyasu S. Bio Protoc. PMID: 33659488 - Tumor-Derived Lactic Acid Contributes to the Paucity of Intratumoral ILC2s.
Wagner M, Ealey KN, Tetsu H, Kiniwa T, Motomura Y, Moro K, Koyasu S. Cell Rep. PMID: 32101749
2019
- Blockade of Lymphangiogenesis Shapes Tumor-Promoting Adipose Tissue Inflammation.
Wagner M, Steinskog ES, Wiig H. Am J Pathol. PMID: 31369756 - Cancer Immunoediting by Innate Lymphoid Cells.
Wagner M, Koyasu S. Trends Immunol. PMID: 30992189 - Hide and seek: Plasticity of innate lymphoid cells in cancer.
Bald T, Wagner M, Gao Y, Koyasu S, Smyth MJ. Semin Immunol. PMID: 30979591
2017
- Lymphangiogenesis Facilitates Initial Lymph Formation and Enhances the Dendritic Cell Mobilizing Chemokine CCL21 Without Affecting Migration.
Karlsen TV, Reikvam T, Tofteberg A, Nikpey E, Skogstrand T, Wagner M, Tenstad O, Wiig H. Arterioscler Thromb Vasc Biol. PMID: 28935759 - Plastic Heterogeneity of Innate Lymphoid Cells in Cancer.
Wagner M, Moro K, Koyasu S. Trends Cancer. PMID: 28718410
2016
- Lymphatic vessels regulate immune microenvironments in human and murine melanoma.
Lund AW*, Wagner M*, Fankhauser M, Steinskog ES, Broggi MA, Spranger S, Gajewski TF, Alitalo K, Eikesdal HP, Wiig H, Swartz MA. J Clin Invest. PMID: 27525437 - Impaired lymphatic function accelerates cancer growth.
Steinskog ES, Sagstad SJ, Wagner M, Karlsen TV, Yang N, Markhus CE, Yndestad S, Wiig H, Eikesdal HP. 2016. PMID: 27329584
2015
- Intercellular transfer of transferrin receptor by a contact-, Rab8-dependent mechanism involving tunneling nanotubes.
Burtey A, Wagner M, Hodneland E, Skaftnesmo KO, Schoelermann J, Mondragon IR, Espedal H, Golebiewska A, Niclou SP, Bjerkvig R, Kögel T, Gerdes HH. FASEB J. PMID: 26220176 - Tumor Interstitial Fluid Formation, Characterization, and Clinical Implications.
Wagner M, Wiig H. Front Oncol. PMID: 26075182 - Adipose tissue macrophages: the inflammatory link between obesity and cancer?
Wagner M, Samdal Steinskog ES, Wiig H. Expert Opin Ther Targets. PMID: 25474374
2014
- A dangerous duo in adipose tissue: high-mobility group box 1 protein and macrophages.
Wagner M. Yale J Biol Med. PMID: 24910558
2013
- Tumor versus stromal cells in culture–survival of the fittest?
Talasila KM, Brekka N, Mangseth K, Stieber D, Evensen L, Rosland GV, Torsvik A, Wagner M, Niclou SP, Mahesparan R, Vintermyr OK, Bjerkvig R, Nigro JM, Miletic H. PLoS One. PMID: 24349039 - Loss of adipocyte specification and necrosis augment tumor-associated inflammation.
Wagner M, Bjerkvig R, Wiig H, Dudley AC. 2013. PMID: 23991365 - A three-party alliance in solid tumors: Adipocytes, macrophages and vascular endothelial cells.
Wagner M, Dudley AC. 2013. PMID: 23805401 - Increased interstitial protein because of impaired lymph drainage does not induce fibrosis and inflammation in lymphedema.
Markhus CE, Karlsen TV, Wagner M, Svendsen ØS, Tenstad O, Alitalo K, Wiig H. Arterioscler Thromb Vasc Biol. PMID: 23288156
2012
- Tumor vasculature: the Achilles’ heel of cancer?
Johannessen TC, Wagner M, Straume O, Bjerkvig R, Eikesdal HP. Expert Opin Ther Targets. 2013 Jan;17(1):7-20. doi: 10.1517/14728222.2013.730522. Epub 2012 Nov 2.PMID: 23121690 - Vasostatin increases oxygenation of B16-F10 melanoma tumors and raises therapeutic efficacy of cyclophosphamide.
Cichoń T, Jarosz M, Smolarczyk R, Ogórek B, Matuszczak S, Wagner M, Mitrus I, Sochanik A, Jazowiecka-Rakus J, Szala S. Acta Biochim Pol. PMID: 22946026 - Inflamed tumor-associated adipose tissue is a depot for macrophages that stimulate tumor growth and angiogenesis.
Wagner M, Bjerkvig R, Wiig H, Melero-Martin JM, Lin RZ, Klagsbrun M, Dudley AC. 2012. PMID: 22614697
2009
- Lysosomal ceramide mediates gemcitabine-induced death of glioma cells.
Dumitru CA, Sandalcioglu IE, Wagner M, Weller M, Gulbins E. J Mol Med (Berl). PMID: 19763526
We are grateful to the following agencies for their generous support of our work.
If you are interested in joining our team, contact us at: marek.wagner@port.lukasiewicz.gov.pl
We are located at:
Łukasiewicz Research Network –
PORT Polish Center for Technology Development,
Life Sciences and Biotechnology Center,
Innate Immunity Research Group,
Stabłowicka 147, 54-066 Wrocław, Poland