Influence of microenvironment on anti-tumor immune response

Tumors cells (light-gray) surrounded by sympathetic nerve (Tyrosine hydroxylase, red)

 Principal Investigator: Vincent Feuillet

Vincent.feuillet@inserm.fr  +33 (0)1 40 51 65 56

Objective

The tumor microenvironment has a major effect on tumor growth and the establishment of an associated immune response. It includes inflammatory mediators, hormones and neurotransmitters. Local secretion of these factors may be related to tumor development itself but may also depend on external events, such as psychological stress. We study the immunosuppressive effects of these mediators and try to understand by which mechanisms they alter T-cell reactivity.

The group

Vincent Feuillet: CR1 Inserm

Ralitsa Stoeva: Master 2

Research interests

Among the molecules of the microenvironment that may influence tumor growth, prostaglandin E2 (PGE2), adenosine and adrenaline have well known pro-tumor effects. Although it is generally admitted that these factors directly promote tumor growth, we believe that their pro-tumor effect could also be due to their action on the immune response and more specifically to their ability to alter T cells reactivity. Indeed, these mediators have in common the capacity to induce sustained increases in intracellular cAMP, a molecule whose immunosuppressive effect on T response is well demonstrated.

In this context, our research focuses on two areas:

1. We want to better understand the influence of stress, and the associated production of neurotransmitters, on the anti-tumor immune response. Using specific antagonists, the effect of these mediators on tumor growth and on associated anti-tumor immune response is evaluated in vivo in mouse models of tumor development.
2. In parallel, we perform imaging experiments on tumor slices. Using a fluorescent probe to measure cAMP on single cells in real time, we evaluate the influence of the tumor microenvironment and candidate molecules to induce a sustained increase in intracellular cAMP in T cells. We will also test whether blocking these mediators (receptors or cAMP pathway downstream) may restore the reactivity of these lymphocytes.

Publications marquantes et brevets (Main publications and patents)

Soutiens financiers

These programs are supported by La Ligue contre le cancer