Immunity and Cancer

Team Manager (DR2)

Jacques Nunès

Project members :

Geoffrey Guittard
Group Manager

Sonia Pastor
Engineer

Iliana Loffreda
Doctoral student

Maria-Victoria Regge
Post-doctoral researcher

Cancer immunotherapy has benefited from the development of approaches targeting tumor-infiltrating cytotoxic lymphocytes, such as immune checkpoint inhibitors and adoptive transfer of immune cells.

Our aim is to propose new strategies to increase the efficacy of current cancer treatments.
We are taking advantage of our expertise in lymphocyte signalling and the tools developed in our team to focus our project on :

• identification of signaling molecules involved in the feedback of signals encoded by activating receptors (TCR, NCR...) in cytotoxic lymphocytes,
• decipher the cooperative action of immune cells and environmental factors such as nutrition against tumors.

GROUP MANAGER

Daniel Olive

Project members :

Luc Xerry
Project manager

Anne-Sophie Chrétien
Group Manager

Caroline Imbert
Post-doctoral researcher

Post-doctoral fellow

Aude Le Roy
Engineer

Alexandrine Faivre
Engineer

Amira Ben Amara
Engineer

Olivier Turrini
Lecturer-Researcher-Hospital practitioner

Philippe Rochigneux
Project manager

Gwenaëlle Gravis-Mescam
Project manager

Florent Amatore
Post-doctoral Hospital Practitioner

Emilien Billon
Post-doctoral Hospital Practitioner

Jonathan Garnier
Post-doctoral Hospital Practitioner

Nicolas Boucherit
Engineer

Oumar Mouctar Diallo
Doctoral student

Téo Fernez
Doctoral student

Pauline Maby
Post-doctoral researcher

Diane Rattier
Engineer

Théo Wirth
Doctoral student

Yara Rym El-Hawly
Master 2 student

Clemence Quere
Master 2 student

Alexia Fleurial
Master 2 student

Chloe Reine
Master 2 student

We are analyzing the alterations in innate immunity associated with cancers and chronic viral infections, and ways of counteracting them through biotherapies. We are also investigating the functions of molecules belonging to the CD28/B7 (CD28, CTLA-4, PD-1, ICOS, BTLA and their ligands CD80, CD86, PD-L1, PD-L2 and ICOSL, as well as the new BTN3A family) and TNF/TNR (HVEM/TNFRSF14, LIGHT/TNFSF14) families, which are involved in regulating immune responses and are preferred therapeutic targets for inhibiting cancer-associated immunosuppression.

Our preferred tools are monoclonal antibodies and recombinant proteins.

Team manager

Raynier Devillier

Project members :

Lea Laban
Engineer

Mingyang Wang
Master 2 student

The allogeneic transplantation team's main focus is on modulating the immunological response to hematopoietic stem cell transplants after reduced-toxicity conditioning, with the aim of establishing an allogeneic immunotherapy platform for further developments.
Several Phase I/II programs are currently underway to boost the anti-tumor response within the first 100 days of transplantation:

• Vaccination with WT1 protein and adjuvant (supported by a PHRC)
• Infusion of donor NK cells after ex-vivo activation (supported by a PHRC)
• administration of an anti-KIR antibody to overcome NK cell inhibition (supported by an ARC project)
• Use of immunomodulating molecules (Lenalidomide).

Group Manager

Caroline Gaudy

Project members :

Jiliana Monnier
Hospital practitioner

Nausicaa Malissen
Teacher-Researcher-Hospital Practitioner

Rabih Chamas
Engineer

Identifying biomarkers of response and toxicity is a major challenge for optimizing and personalizing treatments for melanoma patients. Our main area of research concerns the identification of blood and tissue biomarkers of response and toxicity to immunotherapies in melanoma patients.
We analyze the impact of common biological variables and the evolution of different cell populations before and during treatment, using various techniques for phenotypic characterization of circulating immune populations and quantification of soluble factors. We also study the tumor microenvironment using multiplex tissue analysis.

Group Manager

Alice Carrier

Project members :

Scarlett Gallardo Arriaga
Doctoral student

Margot Morlan
Master 2 student

Pancreatic ductal adenocarcinoma (PDAC) is a lethal, late-diagnosed cancer that is resistant to current therapies, including immunotherapy (IT). This resistance is partly explained by the metabolic reprogramming of the tumor and the presence of an immunosuppressive tumor microenvironment (TME). One mechanism of immunosuppression that remains to be explored is the metabolic reprogramming of immune cells (which directs their function and fate) in the tumor microenvironment and peripherally in distant organs such as muscle (which melts in the majority of PDAC patients). Recent literature suggests that drugs targeting cancer cell metabolism could improve IT by counteracting the metabolic reprogramming of MCT and immunosuppression.

Our laboratory has demonstrated that energy metabolism contributes to the therapeutic resistance of PDAC and is now exploring its role in immunosuppression to improve therapies. In our current project, we hypothesize that targeting metabolism will attenuate immunosuppression and increase the efficacy of IT.

Our objectives are to evaluate the impact of chemotherapy and drugs targeting energy metabolism, in combination with physical activity, on immunometabolism and response to IT. This research project will be carried out in a preclinical context using PDAC mouse models through an integrative study at tissue, cellular and molecular levels.