Functional mapping of CD8+ Tissue-Resident Memory cell / antigen-presenting cell interactions in tumors and healthy tissues – TRMaps

While research efforts focused on CD8+ T activation in lymph node and trafficking to tumors, little is known on CD8+ Tissue-Resident Memory (TRM) cell function at the tumor site. In this proposal, we will measure CD8+TRM cytotoxic capacities at the single cell level, in human non-small cell lung cancers and breast cancers. We hypothesize that some antigen presenting cells (APC) are able to (re)activate CD8+TRM cell locally in tissues, while others might inhibit them. I will combine my tissue 3D-imaging skills with the expertise of the team on human CD8+ T cell activation to draw functional maps of APC/CD8+ TRM interactions in tumoral and surrounding healthy tissues. Furthermore, we will analyse the impact of immunotherapies on these interactions ex-vivo and in cancer patients treated with neoadjuvant therapies. Our results will provide a new global vision of CD8+TRM functions and regulation in cancers. TRMaps project aims to inspire new strategies to potentiate local CD8+TRM anti-tumoral responses.