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April 27th: Yenkel Grinberg & Gaelle Martin talk
27 April 2017 @ 13 h 30 min - 14 h 30 min UTC+1
Yenkel Grinberg & Gaelle Martin (from NYC) will give a conference to present their work.
Title of the Grinberg’s talk: Selective contributions of NF-kB subunits to regulatory T cell biology.
Abstract: Cancers use a wide variety of mechanisms to dampen tumor immune response. Among them, CD4+Foxp3+ regulatory T cells (Tregs) are largely described to inhibit the function of effector cells. Therefore, precisely understanding the mechanisms governing Treg homeostasis may be a valuable strategy to enhance immune responses against cancer. It is established that transcription factor NF-kB plays a major role in Treg development; we are now analyzing the role of canonical p65 and c-Rel NF-kB subunits in mature Tregs. We found that specific ablation of one or both NF-kB subunits in Tregs drove a gradual autoimmune syndrome. This was associated with profound changes in the molecular signature of NF-kB deficient Tregs, which down-regulated Treg-associated genes while acquiring an effector-like phenotype. Mechanistically, ChIP-Seq analyses showed that Foxp3 and NF-kB cooperated to establish a lineage-specific transcriptome. We next explored the role of NF-kB in Treg homeostasis during tumor growth. Strikingly, melanoma growth was drastically reduced in mice lacking c-Rel, but not p65, in Tregs. This was associated with an increased effector T cell activation. Moreover, chemical inhibition of c-Rel delayed melanoma growth and potentiated anti-PD-1 checkpoint-blockade therapy by impairing the Treg transcriptional program.Our data demonstrate a specific role for each NF-kB subunit in Treg function and homeostasis, and highlights a new therapeutic opportunity for the treatment of cancer.
Personal statement here.
Title of the Martin talk: CD97 is a critical regulator of acute myeloid leukemia stem cell function
Despite significant efforts to improve therapies for acute myeloid leukemia (AML), clinical outcomes remain poor. Understanding the mechanisms that regulate the development and maintenance of leukemic stem cells (LSC) is important to reveal new therapeutic opportunities. We have identified CD97, a member of the adhesion class of G-protein coupled receptors (GPCRs), as a frequently upregulated antigen of AML blasts that is a critical regulator of blast function. High levels of CD97 correlate with poor prognosis, and silencing of CD97 reduces disease aggressiveness in vivo. These phenotypes are due to CD97’s function to promote proliferation, survival, and the maintenance of the undifferentiated state in leukemic blasts. Collectively, our data credential CD97 as a promising therapeutic target on LSCs in AML.
Personal statement here.