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Recent publications Breckpot Group

A synthetic DNA template for fast manufacturing of versatile single epitope mRNA


Mol Ther Nucleic Acids. 2022 Aug 17;29:943-954. doi: 10.1016/j.omtn.2022.08.021. eCollection 2022 Sep 13.


A flexible, affordable, and rapid vaccine platform is necessary to unlock the potential of personalized cancer vaccines in order to achieve full clinical efficiency...

mRNA-LNP vaccines tuned for systemic immunization induce strong antitumor immunity by engaging splenic immune cells


Mol Ther. 2022 Sep 7;30(9):3078-3094. doi: 10.1016/j.ymthe.2022.07.007. Epub 2022 Jul 12.


mRNA vaccines have recently proved to be highly effective against SARS-CoV-2. Key to their success is the lipid-based nanoparticle (LNP), which enables efficient mRNA expression and...

Emerging applications of nanobodies in cancer therapy


Int Rev Cell Mol Biol. 2022;369:143-199. doi: 10.1016/bs.ircmb.2022.03.010. Epub 2022 May 18.


Cancer is a heterogeneous disease, requiring treatment tailored to the unique phenotype of the patient's tumor. Monoclonal antibodies (mAbs) and variants thereof have enabled...

Inhibiting Histone and DNA Methylation Improves Cancer Vaccination in an Experimental Model of Melanoma


Front Immunol. 2022 May 12;13:799636. doi: 10.3389/fimmu.2022.799636. eCollection 2022.


Immunotherapy has improved the treatment of malignant skin cancer of the melanoma type, yet overall clinical response rates remain low. Combination therapies could be key to meet this...

RNA in Cancer Immunotherapy: Unlocking the Potential of the Immune System


Clin Cancer Res. 2022 Sep 15;28(18):3929-3939. doi: 10.1158/1078-0432.CCR-21-3304.


Recent advances in the manufacturing, modification, purification, and cellular delivery of ribonucleic acid (RNA) have enabled the development of RNA-based therapeutics for a broad array...

Oncolytic Herpes Simplex Virus Type 1 Induces Immunogenic Cell Death Resulting in Maturation of BDCA-1<sup>+</sup> Myeloid Dendritic Cells


Int J Mol Sci. 2022 Apr 27;23(9):4865. doi: 10.3390/ijms23094865.


Recently, a paradigm shift has been established for oncolytic viruses (OVs) as it was shown that the immune system plays an important role in the specific killing of tumor cells by OVs. OVs have the...

Targeted Radionuclide Therapy with Low and High-Dose Lutetium-177-Labeled Single Domain Antibodies Induces Distinct Immune Signatures in a Mouse Melanoma Model


Mol Cancer Ther. 2022 Jul 5;21(7):1136-1148. doi: 10.1158/1535-7163.MCT-21-0791.


Targeted radionuclide therapy (TRT) using probes labeled with Lutetium-177 (177Lu) represents a new and growing type of cancer therapy. We studied immunologic changes in response to TRT with...

TNF-α-Secreting Lung Tumor-Infiltrated Monocytes Play a Pivotal Role During Anti-PD-L1 Immunotherapy


Front Immunol. 2022 Apr 14;13:811867. doi: 10.3389/fimmu.2022.811867. eCollection 2022.


Immune checkpoint blockade (ICB) of the PD-1 pathway revolutionized the survival forecast for advanced non-small cell lung cancer (NSCLC). Yet, the majority of PD-L1 + NSCLC patients...

Assessing Tumor-Infiltrating Lymphocytes in Breast Cancer: A Proposal for Combining Immunohistochemistry and Gene Expression Analysis to Refine Scoring


Front Immunol. 2022 Feb 11;13:794175. doi: 10.3389/fimmu.2022.794175. eCollection 2022.


Scoring of tumor-infiltrating lymphocytes (TILs) in breast cancer specimens has gained increasing attention, as TILs have prognostic and predictive value in HER2 + and triple-negative...

CS1-specific single-domain antibodies labeled with Actinium-225 prolong survival and increase CD8+ T cells and PD-L1 expression in Multiple Myeloma


Oncoimmunology. 2021 Nov 9;10(1):2000699. doi: 10.1080/2162402X.2021.2000699. eCollection 2021.


Multiple myeloma (MM) is a hematological malignancy characterized by the presence of clonal plasma cells in the bone marrow niche. Despite significant therapeutic advances, MM...

Unraveling the Effects of a Talimogene Laherparepvec (T-VEC)-Induced Tumor Oncolysate on Myeloid Dendritic Cells


Front Immunol. 2021 Oct 28;12:733506. doi: 10.3389/fimmu.2021.733506. eCollection 2021.


T-VEC, a HSV-1 derived oncolytic virus, is approved for the treatment of advanced melanoma. The mechanisms that underly the systemic anti-tumor effect that is seen following...

T-cell subsets in the skin and their role in inflammatory skin disorders


Allergy. 2022 Mar;77(3):827-842. doi: 10.1111/all.15104. Epub 2021 Oct 6.


T lymphocytes (T cells) are major players of the adaptive immune response. Naive T cells are primed in the presence of cytokines, leading to polarization into distinct T-cell subsets with specific...

Formatting and gene-based delivery of a human PD-L1 single domain antibody for immune checkpoint blockade


Mol Ther Methods Clin Dev. 2021 Jun 4;22:172-182. doi: 10.1016/j.omtm.2021.05.017. eCollection 2021 Sep 10.


Monoclonal antibodies that target the inhibitory immune checkpoint axis consisting of programmed cell death protein 1 (PD-1) and its ligand, PD-L1, have changed...

Site-Specific Radiolabeling of a Human PD-L1 Nanobody via Maleimide-Cysteine Chemistry


Pharmaceuticals (Basel). 2021 Jun 8;14(6):550. doi: 10.3390/ph14060550.


Immune checkpoint inhibitors targeting the programmed cell death-1 (PD-1) and its ligand PD-L1 have proven to be efficient cancer therapies in a subset of patients. From all the patients with various...

The antigen-binding moiety in the driver's seat of CARs


Med Res Rev. 2022 Jan;42(1):306-342. doi: 10.1002/med.21818. Epub 2021 May 24.


Immuno-oncology has been at the forefront of cancer treatment in recent decades. In particular immune checkpoint and chimeric antigen receptor (CAR)-T cell therapy have achieved spectacular...

Recent publication Movahedi Group

Single-cell RNA and protein profiling of immune cells from the mouse brain and its border tissues


Nat Protoc. 2022 Oct;17(10):2354-2388. doi: 10.1038/s41596-022-00716-4. Epub 2022 Aug 5.


Brain-immune cross-talk and neuroinflammation critically shape brain physiology in health and disease. A detailed understanding of the brain immune landscape is essential for...

Macrophage compartmentalization in the brain and cerebrospinal fluid system


Sci Immunol. 2022 Mar 4;7(69):eabk0391. doi: 10.1126/sciimmunol.abk0391. Epub 2022 Mar 4.


Macrophages reside within the diverse anatomical compartments of the central nervous system (CNS). Within each compartment, these phagocytes are exposed to unique combinations of...

Comparative analysis of antibody- and lipid-based multiplexing methods for single-cell RNA-seq


Genome Biol. 2022 Feb 16;23(1):55. doi: 10.1186/s13059-022-02628-8.


BACKGROUND: Multiplexing of samples in single-cell RNA-seq studies allows a significant reduction of the experimental costs, straightforward identification of doublets, increased cell throughput, and...

Imaging of Glioblastoma Tumor-Associated Myeloid Cells Using Nanobodies Targeting Signal Regulatory Protein Alpha


Front Immunol. 2021 Nov 30;12:777524. doi: 10.3389/fimmu.2021.777524. eCollection 2021.


Glioblastoma (GBM) is the most common malignant primary brain tumor. Glioblastomas contain a large non-cancerous stromal compartment including various populations of tumor-associated...

MMP2 Modulates Inflammatory Response during Axonal Regeneration in the Murine Visual System


Cells. 2021 Jul 2;10(7):1672. doi: 10.3390/cells10071672.


Neuroinflammation has been put forward as a mechanism triggering axonal regrowth in the mammalian central nervous system (CNS), yet little is known about the underlying cellular and molecular players connecting...

CSF1R inhibition rescues tau pathology and neurodegeneration in an A/T/N model with combined AD pathologies, while preserving plaque associated microglia


Acta Neuropathol Commun. 2021 Jun 8;9(1):108. doi: 10.1186/s40478-021-01204-8.


Alzheimer's disease (AD) is characterized by a sequential progression of amyloid plaques (A), neurofibrillary tangles (T) and neurodegeneration (N), constituting ATN pathology. While microglia...

Targeted Repolarization of Tumor-Associated Macrophages via Imidazoquinoline-Linked Nanobodies


Adv Sci (Weinh). 2021 Mar 8;8(10):2004574. doi: 10.1002/advs.202004574. eCollection 2021 May.


Tumor-associated macrophages (TAMs) promote the immune suppressive microenvironment inside tumors and are, therefore, considered as a promising target for the next generation of...

Single-cell profiling of myeloid cells in glioblastoma across species and disease stage reveals macrophage competition and specialization


Nat Neurosci. 2021 Apr;24(4):595-610. doi: 10.1038/s41593-020-00789-y. Epub 2021 Mar 29.


Glioblastomas are aggressive primary brain cancers that recur as therapy-resistant tumors. Myeloid cells control glioblastoma malignancy, but their dynamics during disease...

Therapeutic depletion of CCR8<sup>+</sup> 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.


BACKGROUND: Modulation and depletion strategies of regulatory T cells (Tregs) constitute valid approaches in antitumor immunotherapy but suffer from severe adverse effects due to their lack of...

Monocytic myeloid-derived suppressor cells home to tumor-draining lymph nodes via CCR2 and locally modulate the immune response


Cell Immunol. 2021 Apr;362:104296. doi: 10.1016/j.cellimm.2021.104296. Epub 2021 Jan 30.


Efficient priming of anti-tumor T cells requires the uptake and presentation of tumor antigens by immunogenic dendritic cells (DCs) and occurs mainly in lymph nodes draining the...

A Binary Cre Transgenic Approach Dissects Microglia and CNS Border-Associated Macrophages


Immunity. 2021 Jan 12;54(1):176-190.e7. doi: 10.1016/j.immuni.2020.11.007. Epub 2020 Dec 16.


The developmental and molecular heterogeneity of tissue macrophages is unravelling, as are their diverse contributions to physiology and pathophysiology. Moreover, also given...

Interleukin-10 Prevents Pathological Microglia Hyperactivation following Peripheral Endotoxin Challenge


Immunity. 2020 Nov 17;53(5):1033-1049.e7. doi: 10.1016/j.immuni.2020.09.018. Epub 2020 Oct 12.


Microglia, the resident macrophages of the brain parenchyma, are key players in central nervous system (CNS) development, homeostasis, and disorders. Distinct brain pathologies...

Tightening the retinal glia limitans attenuates neuroinflammation after optic nerve injury


Glia. 2020 Dec;68(12):2643-2660. doi: 10.1002/glia.23875. Epub 2020 Jul 9.


Increasing evidence suggests that functional impairments at the level of the neurovascular unit (NVU) underlie many neurodegenerative and neuroinflammatory diseases. While being part of the NVU,...

Understanding the glioblastoma immune microenvironment as basis for the development of new immunotherapeutic strategies


Elife. 2020 Feb 4;9:e52176. doi: 10.7554/eLife.52176.


Cancer immunotherapy by immune checkpoint blockade has proven its great potential by saving the lives of a proportion of late stage patients with immunogenic tumor types. However, even in these sensitive tumor types,...

Identifying the variables that drive tamoxifen-independent CreERT2 recombination: Implications for microglial fate mapping and gene deletions


Eur J Immunol. 2020 Mar;50(3):459-463. doi: 10.1002/eji.201948162. Epub 2019 Dec 11.


Ligand-dependent Cre recombinases such as the CreERT2 system allow for tamoxifen-inducible Cre recombination. Important examples are the Cx3cr1-CreERT2 and Sall1-CreERT2 lines that are...

Stromal-targeting radioimmunotherapy mitigates the progression of therapy-resistant tumors


J Control Release. 2019 Nov 28;314:1-11. doi: 10.1016/j.jconrel.2019.10.024. Epub 2019 Oct 15.


Radioimmunotherapy (RIT) aims to deliver a high radiation dose to cancer cells, while minimizing the exposure of normal cells. Typically, monoclonal antibodies are used to...

A single-cell atlas of mouse brain macrophages reveals unique transcriptional identities shaped by ontogeny and tissue environment


Nat Neurosci. 2019 Jun;22(6):1021-1035. doi: 10.1038/s41593-019-0393-4. Epub 2019 May 6.


While the roles of parenchymal microglia in brain homeostasis and disease are fairly clear, other brain-resident myeloid cells remain less well understood. By dissecting border...

Single-domain antibody fusion proteins can target and shuttle functional proteins into macrophage mannose receptor expressing macrophages


J Control Release. 2019 Apr 10;299:107-120. doi: 10.1016/j.jconrel.2019.02.023. Epub 2019 Feb 21.


The tumor microenvironment of numerous prevalent cancer types is abundantly infiltrated with tumor-associated macrophages (TAMs). Macrophage mannose receptor (MMR or CD206)...

Clinical Translation of [<sup>68</sup>Ga]Ga-NOTA-anti-MMR-sdAb for PET/CT Imaging of Protumorigenic Macrophages


Mol Imaging Biol. 2019 Oct;21(5):898-906. doi: 10.1007/s11307-018-01302-5.


PURPOSE: Macrophage mannose receptor (MMR, CD206) expressing tumor-associated macrophages (TAM) are protumorigenic and was reported to negatively impact therapy responsiveness and is associated...

Targeting Protumoral Tumor-Associated Macrophages with Nanobody-Functionalized Nanogels through Strain Promoted Azide Alkyne Cycloaddition Ligation


Bioconjug Chem. 2018 Jul 18;29(7):2394-2405. doi: 10.1021/acs.bioconjchem.8b00319. Epub 2018 Jun 28.


Tumor-associated macrophages (TAMs) with high expression levels of the Macrophage Mannose Receptor (MMR, CD206) exhibit a strong angiogenic and immune suppressive...

Endothelial C-Type Natriuretic Peptide Acts on Pericytes to Regulate Microcirculatory Flow and Blood Pressure


Circulation. 2018 Jul 31;138(5):494-508. doi: 10.1161/CIRCULATIONAHA.117.033383.


BACKGROUND: Peripheral vascular resistance has a major impact on arterial blood pressure levels. Endothelial C-type natriuretic peptide (CNP) participates in the local regulation of vascular...

RoMo: An efficient strategy for functional mosaic analysis via stochastic Cre recombination and gene targeting in the ROSA26 locus


Biotechnol Bioeng. 2018 Jul;115(7):1778-1792. doi: 10.1002/bit.26594. Epub 2018 Mar 31.


Functional mosaic analysis allows for the direct comparison of mutant cells with differentially marked control cells in the same organism. While this offers a powerful approach for...

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.


Tumors of various histological origins show abundant infiltration of myeloid cells from early stages of disease progression. These cells have a profound impact on antitumor immunity...

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.


Tumor-associated macrophages (TAM) are by now established as important regulators of tumor progression by impacting on tumor immunity, angiogenesis, and metastasis. Hence, a multitude of...

Novel insights in the regulation and function of macrophages in the tumor microenvironment


Curr Opin Oncol. 2017 Jan;29(1):55-61. doi: 10.1097/CCO.0000000000000344.


PURPOSE OF REVIEW: Tumors contain not only cancer cells but also nontransformed types of cells, the stromal cells. A bidirectional interplay exists between transformed and nontransformed cells...

Odorant receptors can mediate axonal identity and gene choice via cAMP-independent mechanisms


Open Biol. 2016 Jul;6(7):160018. doi: 10.1098/rsob.160018.


Odorant receptors (ORs) control several aspects of cell fate in olfactory sensory neurons (OSNs), including singular gene choice and axonal identity. The mechanisms of OR-induced axon guidance have been suggested...

The Ontogeny and Microenvironmental Regulation of Tumor-Associated Macrophages


Antioxid Redox Signal. 2016 Nov 10;25(14):775-791. doi: 10.1089/ars.2016.6704. Epub 2016 May 17.


SIGNIFICANCE: Tumor progression is supported by non-cancerous stromal cells, of which tumor-associated macrophages (TAMs) are prominent constituents. These cells could be...

Tissue-resident versus monocyte-derived macrophages in the tumor microenvironment


Biochim Biophys Acta. 2016 Jan;1865(1):23-34. doi: 10.1016/j.bbcan.2015.06.009. Epub 2015 Jul 2.


The tumor-promoting role of macrophages has been firmly established in most cancer types. However, macrophage identity has been a matter of debate, since several levels of...

Tumor hypoxia does not drive differentiation of tumor-associated macrophages but rather fine-tunes the M2-like macrophage population


Cancer Res. 2014 Jan 1;74(1):24-30. doi: 10.1158/0008-5472.CAN-13-1196. Epub 2013 Nov 12.


Tumor-associated macrophages (TAM) are exposed to multiple microenvironmental cues in tumors, which collaborate to endow these cells with protumoral activities. Hypoxia, caused by...

Tumor-induced myeloid-derived suppressor cell subsets exert either inhibitory or stimulatory effects on distinct CD8+ T-cell activation events


Eur J Immunol. 2013 Nov;43(11):2930-42. doi: 10.1002/eji.201343349. Epub 2013 Aug 25.


Tumor growth coincides with an accumulation of myeloid-derived suppressor cells (MDSCs), which exert immune suppression and which consist of two main subpopulations, known as monocytic...

Nanobody-based targeting of the macrophage mannose receptor for effective in vivo imaging of tumor-associated macrophages


Cancer Res. 2012 Aug 15;72(16):4165-77. doi: 10.1158/0008-5472.CAN-11-2994. Epub 2012 Jun 19.


Tumor-associated macrophages (TAM) are an important component of the tumor stroma and exert several tumor-promoting activities. Strongly pro-angiogenic TAMs that reside in...

Tumor-associated macrophages in breast cancer: distinct subsets, distinct functions


Int J Dev Biol. 2011;55(7-9):861-7. doi: 10.1387/ijdb.113371dl.


Macrophages display remarkable plasticity, allowing these cells to adapt to changing microenvironments and perform functions as diverse as tissue development and homeostasis, inflammation, pathogen clearance...

Mononuclear phagocyte heterogeneity in cancer: different subsets and activation states reaching out at the tumor site


Immunobiology. 2011 Nov;216(11):1192-202. doi: 10.1016/j.imbio.2011.06.007. Epub 2011 Jun 30.


Mononuclear phagocytes are amongst the most versatile cells of the body, contributing to tissue genesis and homeostasis and safeguarding the balance between pro- and anti-...

Different tumor microenvironments contain functionally distinct subsets of macrophages derived from Ly6C(high) monocytes


Cancer Res. 2010 Jul 15;70(14):5728-39. doi: 10.1158/0008-5472.CAN-09-4672. Epub 2010 Jun 22.


Tumor-associated macrophages (TAM) form a major component of the tumor stroma. However, important concepts such as TAM heterogeneity and the nature of the monocytic TAM...

A method for the isolation and purification of mouse peripheral blood monocytes


J Immunol Methods. 2010 Jul 31;359(1-2):1-10. doi: 10.1016/j.jim.2010.04.004. Epub 2010 May 8.


Studies in mice have advanced our understanding of the contribution of monocytes to inflammation and immunity. However, the lack of a straightforward and reliable method for...

Alternatively activated macrophages engage in homotypic and heterotypic interactions through IL-4 and polyamine-induced E-cadherin/catenin complexes


Blood. 2009 Nov 19;114(21):4664-74. doi: 10.1182/blood-2009-05-221598. Epub 2009 Sep 2.


Alternatively activated macrophages (AAMs), triggered by interleukin-4 (IL-4) and IL-13, play a modulating role during Th2 cytokine-driven pathologies, but their molecular armament...

IL-10 dampens TNF/inducible nitric oxide synthase-producing dendritic cell-mediated pathogenicity during parasitic infection


J Immunol. 2009 Jan 15;182(2):1107-18. doi: 10.4049/jimmunol.182.2.1107.


Antiparasite responses are associated with the recruitment of monocytes that differentiate to macrophages and dendritic cells at the site of infection. Although classically activated monocytic cells...

Macrophages, PPARs, and Cancer


PPAR Res. 2008;2008:169414. doi: 10.1155/2008/169414.


Mononuclear phagocytes often function as control switches of the immune system, securing the balance between pro- and anti-inflammatory reactions. For this purpose and depending on the activating stimuli, these cells...

Identification of discrete tumor-induced myeloid-derived suppressor cell subpopulations with distinct T cell-suppressive activity


Blood. 2008 Apr 15;111(8):4233-44. doi: 10.1182/blood-2007-07-099226. Epub 2008 Feb 13.


The induction of CD11b(+)Gr-1(+) myeloid-derived suppressor cells (MDSCs) is an important immune-evading mechanism used by tumors. However, the exact nature and function of MDSCs...

Classical and alternative activation of mononuclear phagocytes: picking the best of both worlds for tumor promotion


Immunobiology. 2006;211(6-8):487-501. doi: 10.1016/j.imbio.2006.06.002. Epub 2006 Jul 21.


Mononuclear phagocytes often function as control switches of the immune system, securing the balance between pro- and anti-inflammatory reactions. For this purpose and depending on...