Anz Lab
Immunoregulation
Prof. Dr. med. David Anz
Research Topics
- Investigate the functional role of CCL22 in immune regulation during homeostasis, cancer and autoimmunity.
- Investigate the impact of innate immune stimulation by toll-like-receptor ligands on CCL22 expression and immune regulation during homeostasis and infection.
- Investigate the role of CCL22 overexpression on autoimmunity and infection.
- Exploit CCL22 and CCR4 targeting to optimize cancer immunotherapy.
Background
The immune system is composed of a complex network ensuring protection against pathogens and eradication of harmfully aberrant cells while maintaining tolerance toward endogenous structures. This balance between immune response and tolerance requires various regulatory mechanisms. Hereby, regulatory T cells (Treg), a specialized population of lymphocytes, play a pivotal role. Their main task, as central element of peripheral immune tolerance, is the suppression of immune cells of both the innate and adaptive immune system.
Thus, an impaired function of Treg can lead to an immune response towards endogenous self-antigens promoting the development of autoimmune diseases. In the context of malignant disease. Treg have been reported to contribute to tumor progression through inhibition of anti-tumor immune response.
The immune suppressive mechanisms Treg apply are numerous and range from the secretion of soluble factors to direct physical interaction with other cells. Therefore, the localization of Treg is critical for their immune suppressive capacity. Chemokines, soluble factors that exert a chemotactic effect on cells whose receptor matches the respective chemokine, are essential mediators of the migration of Treg.
Goals
The overall goal of our research group is to better understand the regulatory mechanisms and function of Treg-attracting chemokines.
In our previous work, we identified the chemokine CCL22 as a major regulator of Treg activity. We have shown that the chemokine CCL22, highly expressed by tumor cells themselves or more often by tumor infiltrating dendritic cells, is substantially involved in the recruitment of Treg to the tumor microenvironment via its interaction with its only known functional receptor CCR4, that is primarily expressed by Treg. Application of Toll-like-receptor ligand or RIG-I-ligand therapy caused a suppression of CCL22 and subsequent Treg migration to the tumor which resulted in reduced tumor size. Further, we could show that under homeostatic conditions CCL22 is mainly expressed by dendritic cells in the lymph node, where it mediates direct interaction between Treg and dendritic cells – an interaction that is essential for their immune suppressive function. In the absence of CCL22, their contacts were reduced in favor for conventional T cells resulting in enhanced immune response to inflammation leading up to autoimmunity, increased vaccination response by marked antigen-specific T cells and reduced tumor size and better survival. Based on these results, we are working on to improve antitumor immunotherapy by targeting the CCL22-CCR4 axis.
Prof. Dr. med. David Anz
Principal Investigator (since 2006)
Dr. med. Ignazio Piseddu
Post-Doc (since 2020)
Jan Gärtig, M. Sc.
doctoral researcher (PhD track) (since 2020)
Nicole Lichter
Dipl.-Biotechnol. (since 2017)
Antonia Beimert
doctoral researcher (MD track, FöFoLe) (since 2021)
Luana Messa
doctoral researcher (MD track, FöFoLe) (since 2023)
Linda Hammann
doctoral researcher (PhD track) (since 2023)
Vanessa Wittmann
doctoral researcher (MD track, FöFoLe) (since 2024)
Catharina Witte
doctoral researcher (MD track, FöFoLe) (since 2025)
Santiago Diaz Almeida
doctoral researcher (PhD track) (since 2026)
Leonie Mutz
doctoral researcher (MD track) (since 2026)
Top Ten Papers
Piseddu I, Gärtig J, Eiber S, Moder S, Thaler R, Thaler M, Gruen J, Vornhülz M, Bahner K, Messa L, Kühnemuth B, Müller J, Schnell K, Beimert A, Perleberg C, Röhrle N, Knott MML, Hammann L, Wittmann V, Layritz P, Rapp M, Bourquin C, Mayerle J, Endres S, Anz D. Innate Immune Activation Is a Strong Suppressor of CCL22 and Impedes Regulatory T Cell-Dendritic Cell Interaction. Immunology 2025, DOI: 10.1111/imm.13926. JIF 4,9
Rapp M, Wintergerst MWM, Kunz WG, Vetter VK, Knott MML, Lisowski D, Haubner S, Moder S, Thaler R, Eiber S, Meyer B, Rohrle N, Piseddu I, Grassmann S, Layritz P, Kuhnemuth B, Stutte S, Bourquin C, von Andrian UH, Endres S, Anz D.
CCL22 controls immunity by promoting regulatory T cell communication with dendritic cells in lymph nodes
Journal of Experimental Medicine 2019, DOI: 10.1084/jem.20170277
JIF 10,9Wiedemann GM, Knott M, Vetter V, Rapp M, Haubner S, Fesseler J, Kühnemuth B, Layritz P, Thaler R, Kruger S, Ormanns S, Mayr D, Endres S, Anz D.
Cancer cell-derived IL-1α induces CCL22 and the recruitment of regulatory T cells
Oncoimmunology 2016, DOI: 10.1080/2162402X.2016.1175794
JIF 6,3Rapp M, Grassmann S, Chaloupka M, Layritz P, Kruger S, Ormanns S, Rataj F, Janssen KP, Endres S, Anz D*, Kobold S*.
C-C chemokine receptor type 4 transduction of T cells enhances interaction with dendritic cells, tumor infiltration and therapeutic efficacy of adoptive T cell transfer
Oncoimmunology 2015, DOI: 10.1080/2162402X.2015.1105428
JIF 6,3
*contributed equallyAnz D, Rapp M, Eiber S, Koelzer VH, Thaler R, Haubner S, Knott M, Nagel S, Golic M, Wiedemann G, Bauernfeind F, Wurzenberger C, Hornung V, Scholz C, Mayr D, Rothenfusser S, Endres S, Bourquin C.
Suppression of intratumoral CCL22 by type I interferon inhibits migration of regulatory T cells and blocks cancer progression.
Cancer Research 2015, Nov 1;75(21):4483-93.
JIF 9,3Heidegger S*, Anz D*, Stephan N, Bohn B, Herbst T, Fendler WP, Suhartha N, Sandholzer N, Kobold S, Hotz C, Eisenaecher K, Radtke-Schuller S, Endres S, Bourquin C.
Virus-associated activation of innate immunity induces rapid disruption of Peyer’s patches in mice.
Blood 2013; 122(15):2591-9.
JIF 9,1
*contributed equallyAnz D, Mueller W, Golic M, Kunz WG, Rapp M, Koelzer VH, Ellermeier J, Ellwart JW, Schnurr M, Bourquin C, Endres S.
CD103 is a hallmark of tumor-infiltrating regulatory T cells.
International Journal of Cancer 2011;129:2417-26.
JIF 4,7Anz D, Koelzer VH, Moder S, Thaler R, Schwerd T, Lahl K, Sparwasser T, Besch R, Poeck H, Hornung V, Hartmann G, Rothenfusser S, Bourquin C, Endres S.
Immunostimulatory RNA blocks suppression by regulatory T cells.
Journal of Immunology 2010; 184:939-46
JIF 6,1Anz D, Thaler R, Stephan N, Waibler Z, Trauscheid JM, Scholz C, Kalinke U, Barchet W, Endres S, Bourquin C.
Activation of melanoma differentiation-associated gene 5 causes rapid involution of the thymus.
Journal of Immunology 2009; 182:6044-50
JIF 6,1Poeck H, Besch R, Maihoefer C, Renn M, Tormo D, Morskaya SS, Kirschnek S, Gaffal E, Landsberg J, Hellmuth J, Schmidt A, Anz D, Bscheider M, Schwerd T, Berking C, Bourquin C, Kalinke U, Kremmer E, Kato H, Akira S, Meyers R, Häcker G, Neuenhahn M, Busch D, Ruland J, Rothenfusser S, Prinz M, Hornung V, Endres S, Tüting T, Hartmann G.
5'-triphosphate-siRNA: turning gene silencing and Rig-I activation against melanoma.
Nature Medicine 2008; 14:1256-63
JIF 29,9
