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The major role of tumor micro environment

SIRIC team
01/23/2019
Partager
In neuroblastoma and rhabdoid tumors
Microenvironnement tumoral

Exploring the tumor microenvironment in neuroblastoma

G Schleiermacher, I Janoueix-Lerosey and F Mechta-Grigoriou

Background: Research suggests that there is a correlation between tumor angiogenesis, metastatic development, amplification of the MYCN oncogene and poor outcome. Preliminary data from the team suggest a role for the activated ALK receptor.

In breast and ovary cancers Fatima Mechta-Grigoriou’s group has demonstrated that mesenchymal cells present in the tumor microenvironment can be divided into different sub-types, some have been shown to exhibit immunosuppressive activity (CAF S1) while others display pro-invasive properties (CAF S4).

Hypothesis: Microenvironment and vasculature are key actors in tumor development. Studying their interaction should enable us to better understand tumor heterogeneity and open new therapeutic perspectives to combat resistance.

Studying the link between spatial and molecular aspects of mesenchymal cells in association with the vasculature analysis should enable us to better understand tumor microenvironment heterogeneity.

Objective: Carry out an integrated analysis of tumor microenvironment and vasculature: determine the proportion of each mesenchymal cell sub-type, study the position of these cell sub-types on tissue sections, compare the composition and repartition of mesenchymal cells with the repartition and quantity of immune cells, characterize the different mesenchymal sub-types at a molecular level.

Immune microenvironment and immunotherapy in rhabdoid tumors

F Bourdeaut, E Piaggio and C Pouponnot

Background: A broad analysis of human rhabdoid tumors revealed the presence of an unexpectedly important immune infiltrate in the tumor mass. In parallel the team has recently show that similar immune infiltrate was also present in mouse rhabdoid tumors. These results are particularly interesting given that spectacular regression has been observed in some patients.

Hypothesis: The immune system could be at the origin of spontaneous remission which would suggest the potential interest of immunotherapy. The established parallel with immune infiltrate in mice highlights the interest of rhabdoid tumor mouse-models for the study of immunotherapy’s impact on the regression of aggressive tumors.

Objective: Test the use of immunotherapy and/or radio-immuno combination therapies for future clinical trials.

Projects of the pediatric cancers program