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Seminar

Monday, 30th, September 2019
15h30
Centre de Recherche - Paris - Amphithéâtre Hélène Martel-Massignac (BDD)

T cell trafficking defect in pancreatic cancer

T cells engineered to express chimeric antigen receptors (CARs) have established efficacy in the treatment of B-cell malignancies, but their relevance in solid tumors remains undefined. As part of the Su2C CAR T translational team, together with Carl June and Shelley Berger, we are working to develop CAR T cell therapy for patients with metastatic pancreatic cancer. These are cancers with a high unmet medical need, and generally considered incurable with present therapies. Profiling PBMC from pancreatic ductal adenocarcinoma patients and age matched healthy controls at baseline using high dimensional CyTOF analysis, we observed skewed T cell differentiation in pancreatic cancer patients, with peripheral blood T cells lacking late effector memory cells (EMRA T cells). These EMRA T cells were found in increased proportions in spleens harvested from these patients. Abnormal body distribution of experienced T cell was confirmed in two animal models of pancreatic cancer, were we could demonstrate that this reflects a trafficking defect of differentiated T cells in the context of pancreatic cancer patients. We are now investigating the mechanisms underlying these observations, as well as their impact on T cell immunity and CAR T cell therapy of pancreatic cancer patients.

Speaker(s)

Cécile Alanio

Wherry lab, Institute for Immunology, Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, USA

Invited by

Sebastian Amigorena
Domain 3 - U932 - Immunity and Cancer

Institut Curie

Olivier Lantz
Domain 3 - U932 - Immunity and Cancer

Institut Curie

Contact

Elodie Mieville

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Learn more

After obtaining a Medical Degree in Medical Biology in 2011, I joined the group of Matthew Albert, at the Institut
Pasteur in Paris, for a Master/PhD thesis. Using tetramers, I developed tools for screening rare antigen-specific
CD8 T cells in humans. I applied these to characterize the preimmune repertoire of healthy donors, and of
patients infected by HCV. Following on observations from the later study, I investigated the trafficking and
function of memory-phenotype inexperienced T cells in CXCR3 and CXCL10 deficient mice. In 2015, I joined the
Milieu Interieur (MI) Project for a PostDoc, where I learnt computational approaches for systemic biology. I
applied these new skills to the study of genetic and environmental determinants of (i) thymic function in healthy
humans, and (ii) humoral and cellular responses to latent infections. I started a second PostDoc in the laboratory
of E. John Wherry at the University of Pennsylvania in September 2017. As part of the Su2C Pancreatic Cancer
Team, I am profiling PBMCs from pancreatic ductal adenocarcinoma patients and age matched healthy controls
using high dimensional CyTOF. Mechanisms underlying critical observations are examined using in vitro
approaches, as well as genetically engineered mice (KPC model). In parallel, I am participating to
immunotherapy development, applying CyTOF panels to CAR T cell trials, with the hope to help identifying
correlates of efficiency of CAR T cell therapy. Together, my hope is to help bridging the gap between basic
science and clinical research with the aim to support the development of fundamental insights into disease,
strategies for patient stratification, and therapeutic interventions. I received the Parker Bridge Scholar Award
2019. I’m excited to be part of the worldwide effort to break away from the uniformity of doing the same thing
over and over, and instead, to create more effective, personalized immunotherapies for cancer patients.