Cancer Biomarkers 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 in barrier tissues, including the skin, lungs, and intestine. Recently, a novel group of innate 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 the protective and pathogenic functions 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.
Using melanoma as a model, we have already found that ILC2s exert an anti-tumor response through the recruitment and activation of eosinophils. In contrast, melanoma cells deploy an array of mechanisms such as 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 tumor developmental stages affect ILCs provide an opportunity to increase our understanding of the mechanisms of tumor development and to identify novel diagnostic and prognostic biomarkers as well as prospective therapeutic targets.
Marek Wagner, Ph.D., principal investigator
Marek Wagner received his Ph.D. 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 tumor growth and progression (Wagner et al., Cell Reports 2020). From January 2022, Marek Wagner is leading the Cancer Biomarkers Research Group at Łukasiewicz – PORT (Wrocław, Poland).
If you are interested in joining our group, contact us at:
- Cancer immunosurveillance by ILC2s. Wagner M, Koyasu S. Trends Cancer. 2022 Oct;8(10):792-794. doi: 10.1016/j.trecan.2022.06.010. Epub 2022 Jul 20.PMID: 35871054
- ILC2s and Adipose Tissue Homeostasis: Progress to Date and the Road Ahead. Misawa T, Wagner M, Koyasu S. Front Immunol. 2022 Jun 16;13:876029. doi: 10.3389/fimmu.2022.876029. eCollection 2022.PMID: 35784368
- 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. Pharmaceutics. 2021 Dec 7;13(12):2105. doi: 10.3390/pharmaceutics13122105.PMID: 34959386
- Innate Lymphoid Cells in Skin Homeostasis and Malignancy.
- Wagner M, Koyasu S. Front Immunol. 2021 Oct 8;12:758522. doi: 10.3389/fimmu.2021.758522. eCollection 2021.PMID: 34691082
- A 3D Skin Melanoma Spheroid-Based Model to Assess Tumor-Immune Cell Interactions. Wagner M, Koyasu S. Bio Protoc. 2020 Dec 5;10(23):e3839. doi: 10.21769/BioProtoc.3839. eCollection 2020 Dec 5.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. 2020 Feb 25;30(8):2743-2757.e5. doi: 10.1016/j.celrep.2020.01.103.PMID: 32101749
- Blockade of Lymphangiogenesis Shapes Tumor-Promoting Adipose Tissue Inflammation. Wagner M, Steinskog ES, Wiig H. Am J Pathol. 2019 Oct;189(10):2102-2114. doi: 10.1016/j.ajpath.2019.06.010. Epub 2019 Jul 29.PMID: 31369756
- Cancer Immunoediting by Innate Lymphoid Cells. Wagner M, Koyasu S. Trends Immunol. 2019 May;40(5):415-430. doi: 10.1016/j.it.2019.03.004. Epub 2019 Apr 14.PMID: 30992189
- Hide and seek: Plasticity of innate lymphoid cells in cancer. Bald T, Wagner M, Gao Y, Koyasu S, Smyth MJ. Semin Immunol. 2019 Feb;41:101273. doi: 10.1016/j.smim.2019.04.001. Epub 2019 Apr 9.PMID: 30979591
- 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. 2017 Nov;37(11):2128-2135. doi: 10.1161/ATVBAHA.117.309883. Epub 2017 Sep 21.PMID: 28935759
- Plastic Heterogeneity of Innate Lymphoid Cells in Cancer. Wagner M, Moro K, Koyasu S. Trends Cancer. 2017 May;3(5):326-335. doi: 10.1016/j.trecan.2017.03.008. Epub 2017 May 2.PMID: 28718410
- 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. 2016 Sep 1;126(9):3389-402. doi: 10.1172/JCI79434. Epub 2016 Aug 15.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. Oncotarget. 2016 Jul 19;7(29):45789-45802. doi: 10.18632/oncotarget.9953.PMID: 27329584
- 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. 2015 Nov;29(11):4695-712. doi: 10.1096/fj.14-268615. Epub 2015 Jul 28.PMID: 26220176
- Tumor Interstitial Fluid Formation, Characterization, and Clinical Implications. Wagner M, Wiig H. Front Oncol. 2015 May 26;5:115. doi: 10.3389/fonc.2015.00115. eCollection 2015.PMID: 26075182
- Adipose tissue macrophages: the inflammatory link between obesity and cancer? Wagner M, Samdal Steinskog ES, Wiig H. Expert Opin Ther Targets. 2015 Apr;19(4):527-38. doi: 10.1517/14728222.2014.991311. Epub 2014 Dec 4.PMID: 25474374
- A dangerous duo in adipose tissue: high-mobility group box 1 protein and macrophages. Wagner M. Yale J Biol Med. 2014 Jun 6;87(2):127-33. eCollection 2014 Jun.PMID: 24910558
- 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. 2013 Dec 2;8(12):e81183. doi: 10.1371/journal.pone.0081183. eCollection 2013.PMID: 24349039
- Loss of adipocyte specification and necrosis augment tumor-associated inflammation. Wagner M, Bjerkvig R, Wiig H, Dudley AC. Adipocyte. 2013 Jul 1;2(3):176-83. doi: 10.4161/adip.24472. Epub 2013 Apr 19.PMID: 23991365
- A three-party alliance in solid tumors: Adipocytes, macrophages and vascular endothelial cells. Wagner M, Dudley AC. Adipocyte. 2013 Apr 1;2(2):67-73. doi: 10.4161/adip.23016.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. 2013 Feb;33(2):266-74. doi: 10.1161/ATVBAHA.112.300384. Epub 2013 Jan 3.PMID: 23288156
- 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. 2012;59(3):377-81. Epub 2012 Sep 3.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. Angiogenesis. 2012 Sep;15(3):481-95. doi: 10.1007/s10456-012-9276-y. Epub 2012 May 22.PMID: 22614697
- Lysosomal ceramide mediates gemcitabine-induced death of glioma cells.
- Dumitru CA, Sandalcioglu IE, Wagner M, Weller M, Gulbins E. J Mol Med (Berl). 2009 Nov;87(11):1123-32. doi: 10.1007/s00109-009-0514-8. Epub 2009 Sep 10.PMID: 19763526