CYTOSKELETON AND CANCER PROGRESSION
activities
The immune system plays a crucial role in preventing and combating cancer. Central to this defense is the direct interaction between cytotoxic lymphocytes and cancer cells through a highly specialised cell-cell interface known as the immunological synapse (IS). The IS has two primary functions: 1. “reading” the signals on the surface of potential cancer cells to determine if they should be eliminated or spared, and 2. killing confirmed target cells in a precise manner, minimising collateral damage to surrounding healthy cells.
Our research group is dedicated to unraveling the complexities of the IS between cytotoxic lymphocytes and cancer cells, with a particular emphasis on the cancer cell side of the IS, which remains poorly understood.
Utilising cutting-edge high-resolution and quantitative cell imaging techniques, we have recently highlighted the crucial role of the actin cytoskeleton in enabling cancer cell resistance to cytotoxic lymphocytes. Our research delves into the molecular underpinnings of this resistance, seeking to uncover how the actin cytoskeleton aids cancer cells in evading immune destruction.
We are committed to translating our findings into innovative therapeutic strategies. By targeting signaling pathways and other key components of the IS, we aim to enhance the efficacy of current immunotherapy approaches, such as immune checkpoint inhibitors and CAR-NK and -T cells, to overcome resistance and improve patient outcomes.
Our ultimate goal is to advance the understanding of the immunological synapse and related resistance mechanisms, contributing to the development of next-generation immunotherapies that harness cytotoxic lymphocytes to eradicate cancer cells more effectively.
Thomas
Projects & clinical trials
- The actin cytoskeleton at the tumour cell side of the immunological synapse. In a series of complementary projects, we explore the mechanisms by which fast polarisation of the actin cytoskeleton of tumour cells to the immunological synapse provides direct resistance against cytotoxic lymphocytes and promotes tumour immune evasion in vivo.
- The invadopodial actin cytoskeleton as a potential target to block cancer invasion and metastasis. In this project, we focus on a family of actin regulatory proteins coordinating the formation of invasive membrane protrusions (also termed invadopodia) and the upregulation of proteases involved in extracellular matrix degradation.
Partners
Featured team members
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Valentina
Delli Zotti Visiting Researcher -
Liza
Filali Postdoctoral Fellow -
Céline
Hoffmann Scientist -
Wanxin
Huang PhD Student -
Takouhie
Mgrditchian Postdoctoral Fellow -
Flora
Moreau Laboratory Technician -
Diogo
Pereira Fernandes PhD Student -
Clément
Thomas Group Leader
Scientific publications
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Is the tumor cell side of the immunological synapse a polarized secretory domain? – 24/09/2024
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A comprehensive guide to study the immunological synapse using imaging flow cytometry – 03/04/2024
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Actin remodeling in autophagy-mediated tumor immune escape, mechanistic aspects – 08/12/2023
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CSPG4 CAR-redirected Cytokine Induced Killer lymphocytes (CIK) as effective cellular immunotherapy for HLA class I defective melanoma – 22/11/2023
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Actin cytoskeleton remodeling at the cancer cell side of the immunological synapse – 21/09/2023
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Correlative light and electron microscopy to explore the lytic immunological synapse between natural killer cells and cancer cells – 05/06/2023
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The Immunological Synapse Part B – 11/07/2023
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Actin cytoskeleton depolymerization increases matrix metalloproteinase gene expression in breast cancer cells by promoting translocation of cysteine-rich protein 2 to the nucleus – 15/05/2023
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Measuring CTL Lytic Granule Secretion and Target Cell Membrane Repair by Fluorescent Lipophilic Dye Uptake at the Lytic Synapse – 28/04/2023
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An integrated workflow for phosphopeptide identification in natural killer cells (NK-92MI) and their targets (MDA-MB-231) during immunological synapse formation – 09/02/2023
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