The following core research theme of the Anatomy and Embryology group is focused on cell death and cancer immunotherapy.
Introduction
Mission
The mission of the Cell Death Investigation and Therapy (CDIT) laboratory is to constantly improve our understanding of the role of different immunogenic cell death (ICD) modalities in cancer and to develop novel experimental cancer cell death-based immunotherapies against tumour progression, tumour relapse, and metastasis.
CDIT laboratory is also a part of the Cancer Research Institute Ghent which unites oncology researchers at UGent and the University Hospital (CRIG).
Research
Our research has enabled us to uncover apoptosis, necroptosis, and ferroptosis immunogenicity.
As such, we have identified and characterized different cancer ICD modalities, and developed novel photodynamic therapy ICD-based approaches for a novel more efficient cell-based cancer immunotherapy.
Our ongoing projects focus on further improving ICD and photodynamic therapy-based strategies, bringing them to the clinic and increasing the fundamental understanding of the interaction of cancer cells undergoing ICD with other cell types within the tumour microenvironment.
Instruments
The CDIT laboratory is equipped with state-of-the-art instruments for cell and tissue culture (CO2 incubators, laminar flows, centrifuges, light microscopes) and molecular biology (western blotting, PCR, and DNA gel electrophoresis, SYNGENE gel doc system).
Moreover, the CDIT laboratory has also a unique TECAN Spark20M multimode microplate reader with gas and temperature control modules allowing the following detection modes: absorbance (UV/Vis spectrometer); alpha technology, fluorescence intensity (top & bottom), fluorescence polarization, time-resolved fluorescence intensity, luminescence (glow, flash, multicolour), automated live cell imaging – cell counting and confluence.
Recently, the CDIT lab acquired a Spinning Disk Confocal Nikon Ti2 fluorescence microscope (Nikon, Japan) with an automated stage and advanced software. In addition, the CDIT laboratory has access to the core facilities at UGent: Core Flowcytometry, Core Histology, Ghent Light Miscrocopy Core, Animal House, and Small Animal Optical Imaging (INFINITY).
Research Projects
Development of therapeutic strategies to modulate ICD
The type of cancer cell death determines the antitumor immune response and, therefore, contributes to the efficiency of anti-cancer therapy and the long-term survival of patients. We have identified and characterized the immunogenicity, elasticity and microrheology of different cell death modalities.
Within this line of research, the CDIT strives to better understand the molecular mechanisms of ICD in vitro and in cancer mice models and to develop novel strategies to increase the immunogenicity of dying cancer cells to obtain efficient anti-tumour immune responses. In addition, we aim to unravel the mechanobiological properties of ICD in the context of cancer immunotherapy.
funding: Research Foundation (FWO) for PhD Fellowship, FWO project, Interdisciplinary Research Project from Special Research Fund (BOF) of UGent
Cancer cells undergoing ICD and the tumour microenvironment
The type of cancer cell death (e., ICD) determines the anti-tumour immune responses and, thereby, contributes to the efficiency of anti-cancer therapy. However, the tumour microenvironment may positively or negatively affect the therapeutic efficacy of ICD, and consequently the anti-cancer therapy.
The major focus of this CDIT research line is to identify molecular mechanisms and the key elements responsible for the cross-talk between cancer cells undergoing ICD and the cells of the tumour microenvironment. In addition, cancer spheroids are developed to mimic better these interactions in a three-dimensional context.
funding: Research Foundation (FWO) for PhD Fellowship, Special Research Fund (BOF) from UGent for PhD Fellowship, FWO project
Rational design of photodynamic therapy for melanoma and glioblastoma
Photodynamic therapy is a clinically approved, minimally invasive form of anticancer therapy which involves the administration of a photosensitizer, followed by irradiation with a light source leading to the generation of highly reactive oxygen species that kill tumour cells. Our research has enabled us to develop photodynamic therapy-based approaches to efficiently trigger ICD in several cancer cell types including glioblastoma and melanoma, to build and expand our expertise in orthotopic cancer intracranial and sub-cutaneous models and to develop dendritic cells based cancer immunotherapy.
Within this line of research, the CDIT strives to develop combination strategies based on photodynamic therapy and nano- and bio-materials for the therapy of melanoma and glioblastoma. In addition, we aim to search for novel and more effective photosensitizers, that can induce ICD in cancer cells.
funding: Concerted Research Action (GOA) project from Special Research Fund (BOF) Ghent University; FWO/FNRS “Excellence of Science” project
Polyunsaturated fatty acids in ICD and anti-cancer therapy
Cancer often acquires resistance to conventional therapy including to induction of specific pathways such as apoptosis. Killing cancer cells through other modalities is therefore of utmost interest. Ferroptosis is a recently discovered alternative type of cell death based on the oxidation of specific fatty acids, the well-known omega-3 and -6 polyunsaturated fatty acids (PUFAs). Dietary PUFAs lead to insufficient concentrations in human tumours to profoundly impact cancer progression. In addition, we have proposed that photodynamic therapy may work synergistically with ferroptosis reinforcing each other.
Within this line of research, the CDIT aims by using a combination of ferroptosis induction, PUFAs, and photodynamic therapy to develop effective novel cancer immunotherapy.
