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