Multimodal delineation of a layer of effector function among exhausted CD8 T cells in tumors

Le résumé fourni par la source

Undescribed functional axes may intersect with the trajectory of T cell exhaustion (T EX ) to contribute to the antitumoral functions of CD8 T cells. By leveraging fluorescent transcriptional reporting of the T cell activation marker Cd69 , we defined a classifier for potent versus suboptimal CD69 + activation states arising from T cell stimulation. In tumors, this delineation provided an additional functional readout among T EX subsets, marked by enhanced effector molecule production. The more potent Cd69 -TFP hi state was the most prominent in a T cell–mediated tumor clearance model, displaying increased engagement and superior tumor cell killing. Simultaneous analysis of gene and protein expression in human head and neck tumors enabled a similar strategy to identify Cd69 RNA hi CD69 + cells with enhanced functional features compared with Cd69 RNA lo CD69 + cells among intratumoral CD8 T cell subsets. Thus, refining the T cell functional landscape in tumors potentiates the identification of rare, potent effectors that could be leveraged for improving cancer treatment.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.