Dendritic cells and Cancer Immunotherapy
The mission of the Laoui lab is to constantly improve our understanding of the immune compartment in tumors with a particular focus on dendritic cells to develop novel cancer therapies against tumor progression, tumor relapse and metastasis. More specifically, we use the heterogeneity of tumor-derived conventional dendritic cells (cDCs) as a target for therapeutic intervention. Our research has enabled us to uncover the genetic, phenotypic and functional characteristics of immune cell subpopulations in different activation states in the tumor microenvironment. As such, we have identified and characterized different cDC subpopulations in the tumor and proven their utility as a novel cell-based cancer therapy. Our ongoing projects focus on further improving cDC therapy, bringing it to the clinic as well as increasing the fundamental understanding of their activity. Indeed by evaluating interactions with other cell types within the tumor microenvironment, we aim to identify novel combination strategies to unleash the full potential of cDCs as therapeutic target for cancer treatment. These projects allowed us to build and expand our expertise in orthotopic cancer models for breast, lung and ovarian cancer, metastasis models and analysis techniques such as single cell RNA-seq, CITE-seq, advanced flow cytometric analysis and spatial transcriptomics as well as functional ex vivo and in vitro assays.
Areas of Expertise
- Identification of dendritic cell subsets in distinct mouse and human cancers
- Resistance mechanisms to immunotherapy
- Targeting immunosuppressive cells in the tumor microenvironment
- In vivo and ex vivo dendritic cell function
- Rational design of combination strategies for cancer treatment
Technology Transfer Potential
- Clinical implementation of tumor-derived dendritic cell therapy strategies
- Orthotopic models of lung, breast and ovarian cancer
- Generation of spontaneous metastatic models
Selected publications
- Clappaert, E.J. et al. Flt3L therapy increases the abundance of Treg-promoting CCR7 + cDCs in preclinical cancer models. Front Immunol (2023) Visit ➚
- Murgaski, A. et al. Efficacy of CD40 agonists is mediated by distinct cDC subsets and subverted by suppressive macrophages. Cancer Res 82, 3785-3801 (2022). Visit ➚
- Kiss, M. et al. IL1beta Promotes Immune Suppression in the Tumor Microenvironment Independent of the Inflammasome and Gasdermin D. Cancer Immunol Res 9, 309-323 (2021). Visit ➚
- Laoui, D. et al. The tumour microenvironment harbours ontogenically distinct dendritic cell populations with opposing effects on tumour immunity. Nat Commun 7, 13720 (2016). Visit ➚
- Van Overmeire, E. et al. M-CSF and GM-CSF Receptor Signaling Differentially Regulate Monocyte Maturation and Macrophage Polarization in the Tumor Microenvironment. Cancer Res 76, 35-42 (2016). Visit ➚
Bibliography
- Full bibliography Visit ➚
