Lundi
13/12 / 2019

Lundi
04 / 11 / 2019

Séminaire Externe

Lundi
02/12 / 2019

Séminaire Externe

   Susana COELHO                                                                                                                                                                                                                                                            . (Station Biologique deRoscoff,CNRS)                host: Nicolas Goudemand

Mardi
02/12 / 2019

Lundi
04.05/12 / 2019

Séminaire externe

Mardi
04/12 / 2019

Lundç
09 /12 / 2019

Mardi
10 / 12 / 2019

Cancer progression is greatly influenced by a delicate balance between immunity and tolerance to tumors. While effector T cells (Teff) function to destroy tumor cells, their regulatory T cell (Treg) counterparts are powerful inhibitors of anti-tumor activity. The recent success of immunotherapies demonstrates that this balance can be shifted effectively towards enhanced anti-tumor immunity, to delay or even stop cancer progression. However, only a fraction of patients respond to these treatments. Understanding the molecular mechanisms that drive these responses therefore has important implications for the development of improved therapies. We have recently highlighted the selective contributions of NF-kappaB subunits in Treg function during cancer. Genetic and chemical inhibition of NF-kB c-Rel, but not RelA, impaired Treg homeostasis and delayed cancer growth in mouse models, highlighting c-Rel as a promising therapeutic target. Intriguingly, we recently observed that RelA is essential in the function of mouse and human Teff cells in the steady-state and during cancer. Our work provides novel insights in the molecular regulation of immunity and tolerance to cancer, and paves the way to NF-kB subunits-specific targeting therapies.

Mercredi
18 / 12 / 2019

 Giorgio Trinchieri                      

Commensal microorganisms colonize barrier surfaces of all multicellular organisms, including those of humans. For more than 500 million years commensal microorganisms and their hosts have coevolved and adapted to each other. As a result, the commensal microbiota affects many immune and non-immune functions of their hosts, and de facto the two together comprise one metaorganism. The commensal microbiota communicates with the host via biologically active molecules. Recently, it has been reported that microbial imbalance may play a critical role in the development of multiple diseases, such as cancer, autoimmune conditions and increased susceptibility to infection. The commensal microbiota not only may affect the development, progression and immune evasion of cancer but it has also important effects on the response to cancer immune- and chemo-therapy. Myeloid cells are a major component of the tumor microenvironment where they play a dual role inducing anti-tumor immune responses but mostly promoting immune evasion, tumor progression and metastases formation. Myeloid cells respond to environmental factors including signals derived from
commensal microbes that modulate their function and reactivity thus impacting the response to cancer therapy. The mechanism by which the microbiota controls the response to cancer therapy is due in part to priming of the myeloid cells in the tumor microenvironment to produce pro-inflammatory cytokines and reactive oxygen species. Recently several reports have suggested that also in cancer patients treated with immunocheckpoint inhibitors the composition of the microbiota may affect the success of the therapy. In my seminar I will present a critical valuation of published and unpublished clinical data and discuss targeting of the microbiome composition to improve patients’ response to anti-PD1 therapy using diet modification and fecal microbiota transplantation.