Immune cells and macrophages in therapeutically challenging tumors
Our Focus
Our lab mission is to identify the co-evolving features fuelling tumour cells and myeloid cell subsets pro-tumorigenic interactions in the course of cancer progression, therapy response and tumour relapse. Our lab extensive background in glioblastoma and hepatocellular carcinoma has uncovered cell autonomous and non-cell autonomous mechanisms underlying carcinogenesis and the intricacies of evolution of immune cells underlying malignancy and therapy resistance. Using complementary toolboxes ranging from immunocompetent murine models of these diseases, ex vivo and in vitro systems recapitulating the heterotypic communication between tumour and immune cells, patient samples and dataset analyses, we study the heterogeneity of immune cells in the course of tumour progression. The interests of our research can be summarized in the following points:
- Uncovering the mechanistic bases of the coevolution occurring between cancer and immune cells that fuel cancer growth and can we therapeutically harness vulnerabilities in these interactions
- Design novel, efficiently superior cell engineering, chemical immunology centered tools to rewire specific subsets of immune cells and improve current therapeutic approaches
About Leila Akkari
Leila Akkari
My Research
Leila Akkari trained in cellular and molecular biology during a BA at the University of Montpellier in France, and graduated in 2004 before performing a Master in oncology and immunology between Montpellier and Manchester (England). She performed her PhD in health sciences at the Molecular Genetics Institute of Montpellier, CNRS, in HCV-driven liver cancer prior to joining Prof. Johanna Joyce's laboratory at Memorial Sloan Kettering Cancer Center in NYC as a post doc. During this time, she worked on mouse models of brain and pancreatic cancer, primarily focusing on tumor-associated macrophages and their pro-tumorigenic roles in multiple tumor microenvironment.
Since January 2017, Leila Akkari leads a research group at the Netherlands Cancer Institute in Amsterdam that is interested in the microenvironment-mediated mechanisms of tumor maintenance and therapeutic resistance to therapy in brain and liver malignancies. The main focus of her research is to understand and target the dynamic changes in the tumor microenvironment that are associated with cancer malignancy, with a particular interest in macrophages, a highly plastic and heterogenous immune cell type in solid cancers. Her lab uses a plethora of murine models of cancers to develop and test microenvironment- targeted drugs in a stage-dependent and population-dependent manner.
Awards
- 2025: Professorship, Leiden University
- 2025: Ammodo Award for Fundamental Research
- 2020 to 2024: EMBO Young Investigator Programme Awardee
- 2020 to 2024: Vidi Research Grant, NWO, Life Sciences Netherlands
- 2019 to 2023: Selected as Junior Member of Oncode Institute, Netherlands
- 2017 to 2022: Young Investigator Grant, Bas Mulder Award, KWF Dutch Cancer Society
- 2017 to 2022: Cancer Genomics Center, Young Investigator Programme, NWO, Netherlands
- 2014 to 2016: Postdoctoral Fellowship Grant, American Brain Tumor Association
- 2012 to 2014: Brain Tumor Center Postdoctoral Fellowship, MSKCC, New York City
Key Publications
- 2025 | Fasting boosts breast cancer therapy efficacy via glucocorticoid activation | Nuno Padrão et al. | Nature | View publication
- 2025 | Myeloid cell path to malignancy: insights into liver cancer | Christel F. A. Ramirez | Trends in Cancer | View publication
- 2024 | Cancer cell genetics shaping of the tumor microenvironment reveals myeloid cell-centric exploitable vulnerabilities in hepatocellular carcinoma | Christel F. A. Ramirez et al. | Nature Communications | View publication
- 2024 | Macrophage-mediated myelin recycling fuels brain cancer malignancy | Daan J. Kloosterman et al. | Cell | View publication
- 2024 | Protocol for studying macrophage lipid crosstalk with murine tumor cells | Daan J. Kloosterman et al. | STAR Protocols | View publication
- 2023 | CD103+ regulatory T cells underlie resistance to radio-immunotherapy and impair CD8+ T cell activation in glioblastoma | Luuk van Hooren et al. | Nature Cancer | View publication
- 2023 | Macrophages at the interface of the co-evolving cancer ecosystem | Daan J. Kloosterman et al. | Cell | View publication
- 2023 | Study Protocol: PreOperative Brain irradiation in Glioblastoma (POBIG), A phase I trial | Mueez Waqar et al. | Clinical and Translational Radiation Oncology | View publication
- 2022 | Therapy-induced shaping of the glioblastoma microenvironment: Macrophages at play | Johanna Erbani | Seminars in Cancer Biology | View publication
- 2021 | EGFR activation limits the response of liver cancer to lenvatinib | Haojie Jin et al. | Nature | View publication
- 2021 | Multiparametric Analyses of Hepatocellular Carcinoma Somatic Mouse Models and Their Associated Tumor Microenvironment | Daniel Taranto et al. | Current Protocols | View publication
- 2021 | Innate immune cells in the tumor microenvironment | Ming O. Li et al. | Cancer Cell | View publication
- 2020 | Dynamic changes in glioma macrophage populations after radiotherapy reveal CSF-1R inhibition as a strategy to overcome resistance | Leila Akkari et al. | Science Translational Medicine | View publication
- 2019 | Inducing and exploiting vulnerabilities for the treatment of liver cancer | Cun Wang et al. | Nature | View publication
- 2019 | Understanding the Origin and Diversity of Macrophages to Tailor Their Targeting in Solid Cancers | Karoline Kielbassa et al. | Frontiers in Immunology | View publication
- 2016 | The tumor microenvironment underlies acquired resistance to CSF-1R inhibition in gliomas | Daniela F. Quail et al. | Science | View publication
- 2016 | Combined deletion of cathepsin protease family members reveals compensatory mechanisms in cancer | Leila Akkari et al. | Genes & Development | View publication
- 2014 | Distinct functions of macrophage-derived and cancer cell-derived cathepsin Z combine to promote tumor malignancy via interactions with the extracellular matrix | Leila Akkari et al. | Genes & Development | View publication
- 2013 | CSF-1R inhibition alters macrophage polarization and blocks glioma progression | Stephanie M. Pyonteck et al. | Nature Medicine | View publication
Members
| Leila Akkari Group leader | Ammarina Beumer-Chuwonpad Postdoc | Angelina Huseinovic PostDoc |
| Casper Pachocki PhD Student | Claudia de Paulis PhD Student | Eduardo Martin Quintana Research assistant |
| Efi Tsouri PhD candidate | Jana Vidal Teuton Technician | Johanna Erbani Postdoctoral fellow |
| Kiona Bloodshoofd Technician | Lesley Cornet Technician | Naz Kocabay Technician |
| Martina Färber Phd student | Menno Boon Phd Student | Serena Vegna Postdoc fellow |
| Nicolas Camviel Postdoc | Roos Gietelink Technician | Theo Fazali Technician |
| Shanna Handgraaf Phd Student | Iris Bongers Technician |