Public Thesis Defense of Shiqiang XU - LIBST

Endophilin A3-mediated clathrin-independent endocytosis and retrograde transport in cancer cells promote cytotoxic CD8 T cell activation by Shiqiang XU

Mardi 11 mars 2025 à 16h00 - Salle Jean-Baptiste Carnoy - Bâtiment Carnoy - Croix du Sud - 1348 Louvain-la-Neuve

Endocytosis, a fundamental cellular process, facilitates the internalization of extracellular substances and membrane components, maintaining cellular homeostasis and regulating signal transduction. While conventional clathrin-mediated endocytosis (CME) is well understood, the mechanisms of clathrin-independent endocytosis (CIE) remain less explored. Among CIE pathways, the Endophilin A3 (EndoA3)-mediated endocytic route has been identified as critical for the internalization of immunoglobulin-like proteins such as ALCAM in cancer cells. These proteins are involved in immune synapse formation, a polarized structure essential for T cell activation.

This thesis first investigates whether Intercellular Adhesion Molecule 1 (ICAM1), another immunoglobulin-like protein and crucial immune synapse component, is an EndoA3-dependent cargo. Then, we explore the role of EndoA3-mediated endocytosis and retrograde transport in immune synapse formation and its impact on anti-tumor CD8 T cell activation.

Our findings reveal that ICAM1 is indeed internalized through EndoA3-mediated endocytosis and, like ALCAM, undergoes retromer-dependent retrograde transport to the trans-Golgi network (TGN). Disruption of EndoA3-mediated endocytosis and subsequent retrograde transport in cancer cells impairs the recruitment of ICAM1 to the immune synapse and diminishes T cell activation. These results highlight the critical role of EndoA3-mediated endocytosis and retrograde transport in maintaining the polarized distribution of immune synapse components, providing new insights into potential therapeutic strategies for enhancing cancer immunotherapy.

Jury members :

Prof. Pierre Morsomme  (UCLouvain) (Supervisor)

Prof. Henri-François Renard (UNamur) (Supervisor & Secretary)

Prof. Michel Ghislain  (UCLouvain) (Chairperson)

Prof. Marielle Boonen (UNamur) 

Prof. Pierre van der Bruggen (UCLouvain)

Dr. Claire Hivroz (Institut Curie)

Dr. Ludger Johannes (Institut Curie)

Pay attention : the public defense of Shiqiang XU will also take place in the form of a videoconference