The Lauvau laboratory has a broad interest in the mechanistic understanding -cellular and gene regulation- of host protective immune mechanisms in the context of vaccines and microbial pathogen infections (bacteria, viruses and parasites) as well as tumors (breast cancer and T cell leukemia). We will be presenting and discussing new results related to our investigations in two distinct areas related to i) CD8+ T cell differentiation and ii) regulatory T (Treg) cell biology in a new preclinical murine breast tumor model.
We have built experimental systems in mice to assess the roles of cognate antigen on the functional fates of memory CD8 T cells and their ability to mediate host protection. Our goal is to provide a comprehensive understanding of i) how to generate functionally and epigenetically distinct memory CD8 T cells and ii) how to harness memory CD8 T cell protective mechanisms to the benefit of the host for new T cell therapies. We will present and discuss recent unexpected results related to how T cell receptor signals and distinct epitope modes of recognition impact the functional differentiation and fitness of memory CD8+ T cells in vivo.
We are using a new mouse mammary stem cell-based breast tumor model in which known human cancer-driver mutations have been introduced by CRISPR/Cas9 gene editing. These include functional loss of the tumor suppressor genes MLL3 -a histone methyltransferase- and p53, and constitutive PI3-kinase activation, recapitulating a genetic makeup of very aggressive breast cancers. Our goal is to improve our mechanistic understanding of how most frequent combinations of key tumor suppressor mutations and oncogenes alter the tumor immune microenvironment to foster tumorigenesis and promote tumor immune escape. We will present and discuss recent results directly linking MLL3 loss to Foxp3+ Treg cell-infiltration and differentiation into highly suppressive Treg cells in the tumors, and how these findings may represent new therapeutic opportunities for MLL3-mutant breast cancers.

Grégoire Lauvau is invited by Nadège Bercovici.