Laura Vincelet

Lymphatic system is essential for removing fluid and inflammatory cells from inflamed tissues and also plays a role in immune modulations. In solid tumors, it provides routes for metastatic spread and regulates immune cell trafficking and functions on primary tumor environment. However, the mechanisms by which lymphatics control the balance between immune surveillance and immune suppression in tumor context remain unknown. My host laboratory found that an increase of lymphatic vessel density in tumor environment promotes an immune suppressive environment by overexpressing Nectin-2 leading to the formation of enlarged tumors. By a single cell RNA sequencing analysis at carcinoma stages, they found that the suppressive effect of the lymphatic system was attributed to a CCR7-positive subpopulation of naive T cells that overexpress TIGIT immune checkpoint, the Nectin-2 receptor, into the mammary gland.  In particular, they identified a reduced infiltration of CD8+CCR7+ T cell population expressing TIGIT and a decrease of CD8+ T cell cytotoxic functions in tumor environment.

 

During my internship, I will study the effect of TIGIT inhibitors on tumor development. In addition, I will confirm the role of CD8+CCR7+ T cell population by depleting CD8+ Tcells during tumor development. We expect to observe an inhibition of the immune surveillance induced by intratumoral lymphatics leading to a significant reduction of tumor progression.

 

This project aims to demonstrate that tumor-associated lymphatic vessels may control in part the immune suppressive state of tumor microenvironment.