Research Group Dr. Máté Kiss
Neutrophils in Cancer
Our lab investigates the interactions between cancer and neutrophils, one of the most common immune cell types in the human body. Neutrophils are frequently reprogrammed to support cancer progression by suppressing the anti-tumor immune response, promoting tumor vascularization and facilitating metastasis. Accordingly, high neutrophil abundance in tumors is often associated with poor patient outcomes.
However, neutrophils can also acquire functional states that oppose cancer growth through cancer cell killing, T-cell stimulation, or antigen presentation. Cancer immunotherapies targeting T cells can trigger the systemic expansion of such beneficial neutrophils with cytotoxic and immunostimulatory properties, contributing to treatment success.
How these opposing neutrophil functional states arise remains poorly understood.
The goal of our research program is to elucidate the signaling axes, epigenomic programs and transcription factors that drive functionally distinct neutrophil states in cancer. We aim to identify regulatory circuits that control the local response of neutrophils to the tumor microenvironment and the emergence of tumor-supportive functions. In parallel, we aim to elucidate how neutrophils with cytotoxic and immunostimulatory properties arise and identify key regulatory nodes that can be targeted to expand these beneficial neutrophil states in cancer.
To address these research questions, we combine analysis of patient samples, pre-clinical mouse models, CRISPR-based genetic perturbations, as well as transcriptomic, epigenomic and proteomic profiling of neutrophils.
Our long-term goal is to build on the fundamental knowledge we obtain and develop new strategies to therapeutically modulate neutrophil function in cancer.
Epigenomic preconditioning of peripheral monocytes determines their transcriptional response to the tumor microenvironment.
Kiss M, Halasz L, Hadadi E, Berger WK, Tzerpos P, Poliska S, Kancheva D, Gabriel A, Mora Barthelmess R, Debraekeleer A, Brughmans J, Elkrim Y, Martens L, Saeys Y, Daniel B, Czimmerer Z, Laoui D, Nagy L, Van Ginderachter JA.
Genome Med. 2025 Jul 23;17(1):82. doi: 10.1186/s13073-025-01511-y.
A neutrophil response linked to tumor control in immunotherapy.
Gungabeesoon J, Gort-Freitas NA, Kiss M, Bolli E, Messemaker M, Siwicki M, Hicham M, Bill R, Koch P, Cianciaruso C, Duval F, Pfirschke C, Mazzola M, Peters S, Homicsko K, Garris C, Weissleder R, Klein AM, Pittet MJ.
Cell. 2023 Mar 30;186(7):1448-1464.e20.
IL1β Promotes Immune Suppression in the Tumor Microenvironment Independent of the Inflammasome and Gasdermin D.
Kiss M, Vande Walle L, Saavedra PHV, Lebegge E, Van Damme H, Murgaski A, Qian J, Ehling M, Pretto S, Bolli E, Keirsse J, Bardet PMR, Arnouk SM, Elkrim Y, Schmoetten M, Brughmans J, Debraekeleer A, Fossoul A, Boon L, Raes G, van Loo G, Lambrechts D, Mazzone M, Beschin A, Wullaert A, Lamkanfi M, Van Ginderachter JA, Laoui D. Cancer Immunol Res. 2021 Mar;9(3):309-323.
Retinoid X receptor suppresses a metastasis-promoting transcriptional program in myeloid cells via a ligand-insensitive mechanism.
Kiss M, Czimmerer Z, Nagy G, Bieniasz-Krzywiec P, Ehling M, Pap A, Poliska S, Boto P, Tzerpos P, Horvath A, Kolostyak Z, Daniel B, Szatmari I, Mazzone M, Nagy L.
Proc Natl Acad Sci U S A. 2017 Oct 3;114(40):10725-10730.
More Publications
CCL3 is produced by aged neutrophils across cancers and promotes tumor growth
Cancer Cell. 2026 Mar 9;44(3):624-640.e12. doi: 10.1016/j.ccell.2026.01.006. Epub 2026 Feb 5.
ABSTRACT
Tumor-associated neutrophils (TANs) are abundant across cancers,…
Positioning and reversible suppression of CCR7+ dendritic cells in perivascular tumor niches shape cancer immunity
Immunity. 2026 Jan 13;59(1):161-176.e12. doi: 10.1016/j.immuni.2025.11.020. Epub 2025 Dec 19.
ABSTRACT
Tumor-resident CCR7+ dendritic cells (DCs) are key determinants of…
VSIG4 Is Dispensable for Tumor Growth and Metastasis in Murine Colorectal and Breast Cancer Models
Cancers (Basel). 2025 Oct 1;17(19):3207. doi: 10.3390/cancers17193207.
ABSTRACT
BACKGROUND: Tumor-associated macrophages (TAMs) are important contributors to tumor…
Depleting IL1R2+ Tumor-Infiltrating Regulatory T Cells with an ADCC-Prone Nanobody Construct Boosts the Efficacy of Anti-PD-1 Immunotherapy
Cancer Res. 2025 Dec 1;85(23):4681-4700. doi: 10.1158/0008-5472.CAN-24-3095.
ABSTRACT
Eliminating immunosuppressive cells, such as regulatory T cells (Treg), is a…
Epigenomic preconditioning of peripheral monocytes determines their transcriptional response to the tumor microenvironment
Genome Med. 2025 Jul 23;17(1):82. doi: 10.1186/s13073-025-01511-y.
ABSTRACT
BACKGROUND: Monocytes are recruited to tumors and undergo transcriptional reprogramming…
Mitochondrial control of macrophage polarity in tumors
Immunity. 2025 Jul 8;58(7):1618-1620. doi: 10.1016/j.immuni.2025.06.008.
ABSTRACT
Macrophages can foster pro- or anti-tumor immune environments. In this issue of…
VSIG4-Expressing Macrophages Contribute to Antiparasitic and Antimetastatic Responses in the Peritoneal Cavity
Eur J Immunol. 2025 May;55(5):e202551804. doi: 10.1002/eji.202551804.
ABSTRACT
Large peritoneal macrophages (LPMs) play a role as gatekeepers of peritoneal homeostasis…
CXCL9:SPP1 macrophage polarity identifies a network of cellular programs that control human cancers
Science. 2023 Aug 4;381(6657):515-524. doi: 10.1126/science.ade2292. Epub 2023 Aug 3.
ABSTRACT
Tumor microenvironments (TMEs) influence cancer progression but are…
A neutrophil response linked to tumor control in immunotherapy
Cell. 2023 Mar 30;186(7):1448-1464.e20. doi: 10.1016/j.cell.2023.02.032.
ABSTRACT
Neutrophils accumulate in solid tumors, and their abundance correlates with poor…
Junctional adhesion molecule-A is dispensable for myeloid cell recruitment and diversification in the tumor microenvironment
Front Immunol. 2022 Dec 1;13:1003975. doi: 10.3389/fimmu.2022.1003975. eCollection 2022.
ABSTRACT
Junctional adhesion molecule-A (JAM-A), expressed on the surface of…
Efficacy of CD40 Agonists Is Mediated by Distinct cDC Subsets and Subverted by Suppressive Macrophages
Cancer Res. 2022 Oct 17;82(20):3785-3801. doi: 10.1158/0008-5472.CAN-22-0094.
ABSTRACT
Agonistic αCD40 therapy has been shown to inhibit cancer progression in only a…
A growth factor-expressing macrophage subpopulation orchestrates regenerative inflammation via GDF-15
J Exp Med. 2022 Jan 3;219(1):e20210420. doi: 10.1084/jem.20210420. Epub 2021 Nov 30.
ABSTRACT
Muscle regeneration is the result of the concerted action of multiple cell…
Therapeutic depletion of CCR8+ tumor-infiltrating regulatory T cells elicits antitumor immunity and synergizes with anti-PD-1 therapy
J Immunother Cancer. 2021 Feb;9(2):e001749. doi: 10.1136/jitc-2020-001749.
ABSTRACT
BACKGROUND: Modulation and depletion strategies of regulatory T cells (Tregs)…
IL1β Promotes Immune Suppression in the Tumor Microenvironment Independent of the Inflammasome and Gasdermin D
Cancer Immunol Res. 2021 Mar;9(3):309-323. doi: 10.1158/2326-6066.CIR-20-0431. Epub 2020 Dec 23.
ABSTRACT
IL1β is a central mediator of inflammation. Secretion of IL1β…
Systemic Reprogramming of Monocytes in Cancer
Front Oncol. 2020 Sep 17;10:1399. doi: 10.3389/fonc.2020.01399. eCollection 2020.
ABSTRACT
Monocytes influence multiple aspects of tumor progression, including antitumor…
Innate Immune Defense Mechanisms by Myeloid Cells That Hamper Cancer Immunotherapy
Front Immunol. 2020 Jul 9;11:1395. doi: 10.3389/fimmu.2020.01395. eCollection 2020.
ABSTRACT
Over the past decade, cancer immunotherapy has been steering immune…
Lithocholic Acid, a Metabolite of the Microbiome, Increases Oxidative Stress in Breast Cancer
Cancers (Basel). 2019 Aug 27;11(9):1255. doi: 10.3390/cancers11091255.
ABSTRACT
In breast cancer patients, the diversity of the microbiome decreases, coinciding with…
High Salt Inhibits Tumor Growth by Enhancing Anti-tumor Immunity
Front Immunol. 2019 Jun 4;10:1141. doi: 10.3389/fimmu.2019.01141. eCollection 2019.
ABSTRACT
Excess salt intake could affect the immune system by shifting the immune…
Labelled regulatory elements are pervasive features of the macrophage genome and are dynamically utilized by classical and alternative polarization signals
Nucleic Acids Res. 2019 Apr 8;47(6):2778-2792. doi: 10.1093/nar/gkz118.
ABSTRACT
The concept of tissue-specific gene expression posits that lineage-determining…
Diamonds in the Rough: Harnessing Tumor-Associated Myeloid Cells for Cancer Therapy
Front Immunol. 2018 Oct 8;9:2250. doi: 10.3389/fimmu.2018.02250. eCollection 2018.
ABSTRACT
Therapeutic approaches that engage immune cells to treat cancer are becoming…
Myeloid cell heterogeneity in cancer: not a single cell alike
Cell Immunol. 2018 Aug;330:188-201. doi: 10.1016/j.cellimm.2018.02.008. Epub 2018 Feb 14.
ABSTRACT
Tumors of various histological origins show abundant infiltration of…
The Transcription Factor STAT6 Mediates Direct Repression of Inflammatory Enhancers and Limits Activation of Alternatively Polarized Macrophages
Immunity. 2018 Jan 16;48(1):75-90.e6. doi: 10.1016/j.immuni.2017.12.010.
ABSTRACT
The molecular basis of signal-dependent transcriptional activation has been extensively…
Dynamic transcriptional control of macrophage miRNA signature via inflammation responsive enhancers revealed using a combination of next generation sequencing-based approaches
Biochim Biophys Acta Gene Regul Mech. 2018 Jan;1861(1):14-28. doi: 10.1016/j.bbagrm.2017.11.003. Epub 2017 Nov 11.
ABSTRACT
MicroRNAs are important components of the…
Retinoid X receptor suppresses a metastasis-promoting transcriptional program in myeloid cells via a ligand-insensitive mechanism
Proc Natl Acad Sci U S A. 2017 Oct 3;114(40):10725-10730. doi: 10.1073/pnas.1700785114. Epub 2017 Sep 18.
ABSTRACT
Retinoid X receptor (RXR) regulates several key…
Beyond the M-CSF receptor - novel therapeutic targets in tumor-associated macrophages
FEBS J. 2018 Feb;285(4):777-787. doi: 10.1111/febs.14202. Epub 2017 Sep 6.
ABSTRACT
Tumor-associated macrophages (TAM) are by now established as important regulators of…
The tumour microenvironment harbours ontogenically distinct dendritic cell populations with opposing effects on tumour immunity
Nat Commun. 2016 Dec 23;7:13720. doi: 10.1038/ncomms13720.
ABSTRACT
Various steady state and inflamed tissues have been shown to contain a heterogeneous DC population…
The IL-4/STAT6 signaling axis establishes a conserved microRNA signature in human and mouse macrophages regulating cell survival via miR-342-3p
Genome Med. 2016 May 31;8(1):63. doi: 10.1186/s13073-016-0315-y.
ABSTRACT
BACKGROUND: IL-4-driven alternative macrophage activation and proliferation are characteristic…
Genomewide effects of peroxisome proliferator-activated receptor gamma in macrophages and dendritic cells--revealing complexity through systems biology
Eur J Clin Invest. 2015 Sep;45(9):964-75. doi: 10.1111/eci.12491. Epub 2015 Aug 7.
ABSTRACT
BACKGROUND: Systems biology approaches have become indispensable tools in…
The role of lipid-activated nuclear receptors in shaping macrophage and dendritic cell function: From physiology to pathology
J Allergy Clin Immunol. 2013 Aug;132(2):264-86. doi: 10.1016/j.jaci.2013.05.044.
ABSTRACT
Nuclear receptors are ligand-activated transcription factors linking lipid…