Immunité anti-cancéreuse et immunothérapies - Fernand Gallais Conference Room

Dr. Eliane Piaggio

Institut Curie, Paris

Regulatory T cells and cancer: a translational approach

Dr. Eliane Piaggio heads the “Translational immunotherapy” team at the Institut Curie, in Paris. She is an expert in immunotherapy, her field of investigation for around twenty years. Her recent studies focus on the identification of new immunological targets and biomarkers in the tumor microenvironment, tumor-draining lymph nodes, and patient blood. Her team also aims to carry out mechanistic studies in vitro as well as in murine tumor models in order to pre-clinically validate these new therapeutic targets and biomarkers. More precisely, her team’s research program is structured around three main themes:
A) Optimization of anti-tumor immune responses in patients with rhabdoid tumors: a translational approach.
B) Functional and developmental mechanisms of human Tregs in cancer: a multimodal approach based on “single cell omics”.
C) Characterization of the T lymphocyte response to neoantigens in three types of cancer and feasibility study of an “à la carte” vaccine (clinical trial).

Selected references

• Ramos, Missolo-Koussou et al. (2022) Tissue-resident FOLR2+ macrophages associate with CD8+ T cell infiltration in human breast cancer. Cell 185, 1189–1207
• Núñez, Tosello Boari, Ramos et al. Tumor invasion in draining lymph nodes is associated with Treg accumulation in breast cancer patients. Nat Commun 11, 3272 (2020)
• Leruste et al. Clonally Expanded T Cells Reveal Immunogenicity of Rhabdoid Tumors. Cancer Cell 36, 597-612 (2019)

Dr. Christophe Caux

Centre de Recherche en Cancérologie de Lyon

Dendritic cells and NK cells in tumor immune surveillance

Dr. Christophe Caux is an expert in Immunology and leads the “Cancer Immune Surveillance and Therapeutic Targeting” team. His team conducts fundamental and translational research programs focused on breast, ovarian and colon carcinomas aimed at identifying immune escape mechanisms and developing therapeutic strategies to restore anti-tumor immune responses. The team identified interactions between plasmacytoid dendritic cells and regulatory T lymphocytes as a dominant local immunosuppression pathway, and characterized targets for immune intervention (ICOS, CD73).
The team recently initiated a line of research to define the mechanisms of immunosurveillance of pre-neoplastic stages which remain largely under-explored. Using both biased biology and integrative systems biology approaches, the team is looking for innate-intrinsic sensing mechanisms of cellular transformation and extrinsic sensing mechanisms propagating the immune alert across cells of the innate immunity (DC, neutrophils) and adaptive.

Selected references

• Hubert et al. (2020) IFN-III is selectively produced by cDC1 and predicts good clinical outcome in breast cancer. Sci Immunol 5 (46)
• Shekarian et al. (2019) Repurposing rotavirus vaccines for intratumoral immunotherapy can overcome resistance to immune checkpoint blockade. Sci Transl Med 11, eaat5025
• Ramos et al. (2020) CD163+ tumor-associated macrophage accumulation in breast cancer patients reflects both local differentiation signals and systemic skewing of monocytes. Clin Transl Immunol 9(2):e1108

Dr. Philippe Bousso

Institut Pasteur, Paris

Decoding the mode of action of tumor immunotherapies

Dr. Philippe Bousso is an immunologist heading the Dynamics of Immune Responses Unit at the Pasteur Institute. With the help of innovative functional imaging approaches, his research aims at understanding and manipulating immune responses in the context of disease pathogenesis.
Over the last years, his lab helped redefine the process of T cell activation in vivo. His work in the field of infectious diseases offered the first demonstration that effector cytokines were acting over extended distances in the infected tissue to effectively control intracellular pathogens. His lab also characterized a novel cellular pathway responsible for graft rejection.
In the context of tumor immunity, his group identified the distinct roles of T cells and NK cells in tumor cell killing and uncovered the mode of action of anti-CD20 therapy, the most common immunotherapy used to treat B cell lymphomas. Finally, his lab has recently characterized the mode of action of the anti-HIV candidate vaccine MVA.
Selected references

• Boulch et al. A major role for CD4+ T cells in driving cytokine release syndrome during CAR T cell therapy. Cell Rep Med 2023 101161
• Boulch et al. Tumor-intrinsic sensitivity to the pro-apoptotic effects of IFN-γ is a major determinant of CD4+ CAR T-cell antitumor activity. Nat Cancer 2023
• Corre et al. Integration of intermittent calcium signals in T cells revealed by temporally patterned optogenetics. iScience 2023 26(2): 106068