Modélisation du
microenvironnement tumoral:
le paradigme des cancers
MSI-H
Loic Verlingue
MD, PhD student
1 GR Dig 2017
Pattern of response in MSI-H
PD-1 Blockade in Tumors with Mismatch-Repair Deficiency D.T. Le, NEJM, june 2016
Hackl H, Charoentong P, Finotello F, Trajanoski Z. Computational genomics tools for dissecting tumour-immune cell interactions. Nat Rev Genet. 2016 Jul
Deciphering tumor and micro-environment
A problem : mutational load & immune infiltration
Spranger S, et al. Density of immunogenic antigens does not explain the presence or absence of the T-cell-inflamed tumor microenvironment in melanoma. PNAS; 2016;113:E7759–68. Tumor immune microenvironment characterization in clear cell renal cell carcinoma identifies prognostic and immunotherapeutically relevant messenger RNA signatures, Genome biology, 2016
Lynch and POLE syndromes: some are immuno depleted
Nebot-Bral L, Brandao D, Verlingue L, et al. Hypermutated tumours in the era of immunotherapy: The paradigm of personalised medicine. Eur J Cancer. 2017 Oct
Are all MSI Equals ?
MSI CRC
MSI Non-CRC
P
F S
Lynch
Sporadic
P
F S
EL-DAKDOUKI Y, VERLINGUE L et al. Poster #1171P ESMO 2017
CD8+ T-cells > MSI status
Mlecnik B, et al. Immunity. 2016.
Identifying cancer infiltrating immune cells: a new gold standard?
Immune Contexture, Immunoscore, and Malignant Cell Molecular Subgroups for Prognostic and Theranostic Classifications of Cancers, Etienne Becht, Advances in Immunology, Volume 130, 2016
Prognosis impact associated with tumor infiltration by various hematopoietic populations (IHC mainly)
Artifical neural network Molecular interaction network
VS
Ok for face recognition, car driving, finance…
…but biology already has regulation networks!
Verlingue L, et al. A. A comprehensive approach to the molecular determinants of lifespan using a Boolean model of geroconversion. Aging Cell. 2016 Sep
How to integrate such information?
Input
Output
T CD4
IL1/IL6
Macrophages Cancer cells
Dendritic cells
Dynamic regulation networks
Merci pour votre attention