Exploring the role of PlexinA4 en cytotoxic T cells: insights for anti-tumor immune responses and cancer immunotherapy

This project investigates how attractive-repulsive cues, like plexins, play a role in fine-tuning immune cell navigation to drive inflammation into the tumor, leading to a better response to current immune checkpoint inhibitors.

Aims:1 Characterize the expression of PlexinA4 and uncover its functional role in CTLs(WP1-2)

2 Explore the in vivo role of PlexinA4 targeting in CTLs during tumor progression(WP3)

3 Investigate the molecular mechanisme behind this phenotype (WP4)

4 Test PlexinA4-targeted strategies that may help circumventing immunotherapy resistance (WP5)

With this work, we expect to unravel the role of PlexinA4 in CTLs and potentially identify an agonist therapy to generate and amplify T-cell responses in the TME. By overcoming the lack of functional CTLs in the tumor, we aim to test PlexinA4 genetic deletion (or pharmalogic inhibition) with already established immune checkpoint inhibitors to enable optimal immunotherapy