Caractérisation et régulation des cellules immunitaires innées au sein du microenvironnement des cancers épithéliaux

About

The skin and mucous membranes of the oral cavity are immunocompetent epithelial tissues in direct contact with the environment. They are continuously exposed to mutagenic agents and inflammatory molecules. It is now demonstrated that immune dysregulation contributes to the development of inflammatory disorders and cancers within these epithelia.
Recent work conducted by our team on murine models of cutaneous and oral carcinogenesis and on human biopsies has identified immune suppression associated with the progression and aggressive forms of these cancers. In particular, we have shown that:

Building on this work, our ongoing studies focus on characterizing immune responses during the progression of skin and oral cavity carcinomas, integrating spatial data acquired through the innovative approach of mass cytometry imaging. Our research focuses on the interactions between immune cells within tumors and with two types of acellular components: nerves and extracellular matrix proteins. Mapping these microenvironments will allow us to identify predictive biomarkers of recurrence and the efficacy of immunotherapies. The goal is to identify new immunotherapy targets as well as mechanisms of resistance to current immunotherapy treatments.

Myeloid cells such as neutrophils and the macrophages progressively infiltrate precancerous and established lesions and possess a genetic and functional profile that promotes tumor growth through multiple mechanisms (Khou-Popa et al, 2020, Bourdely et al, 2022).
THE conventional NK cells and innate lymphoid cells 1 (ILC1) Infiltrating tumors contribute to the control of precancerous lesions and early tumors but become dysfunctional during tumor progression (Luci-Bihl et al, 2021).
THE regulatory dendritic cells associated with tumors can be reprogrammed by local treatment with protective antitumor DCs (2 patents, 2016), whose mechanisms of action are being studied.
Of the mathematical models Based on partial differential equations, they can summarize the tumor elimination phase, equilibrium, and escape phase in immuno-controlled tumors.Atsou et al, 2020, Atsou et al, 2021These mathematical models are useful tools that identify the most influential parameters and can thus guide therapeutic strategies (Atsou et al, 2022, Fotso et al, 2024).
An innovative approach using mass cytometry imaging (IMC, Hyperion) based on the development of a first panel of antibodies targeting 39 markers allows the exhaustive and integrative characterization of the microenvironment of cutaneous squamous cell carcinomas and oral cavity cancers (Elaldi et al, 2021).