Single-cell transcriptomics identifies multiple pathways underlying antitumor function of TCR- and CD8αβ-engineered human CD4 <sup>+</sup> T cells
Jan A. Rath, Gagan Bajwa, Benoît M. Carrères, Elisabeth Hoyer, Isabelle Gruber, Melisa Martinez-Paniagua, Yi-Ru Yu, Nazila Nouraee, Fatemeh Sadeghi, Meng‐Fen Wu, Tao Wang, Michaël Hebeisen, Nathalie Rufer, Navin Varadarajan, Ping‐Chih Ho, Malcolm K. Brenner, David Gfeller, Caroline Arber
Abstract
T cells were most potent by activating multiple transcriptional programs associated with enhanced antitumor function. We found sustained activation of cytotoxicity, costimulation, oxidative phosphorylation- and proliferation-related genes, and simultaneously reduced differentiation and exhaustion. Our study identifies molecular features of TCR8 expression that can guide the development of enhanced immunotherapies.
Topics & Concepts
T-cell receptorCytotoxic T cellCD8Cell biologyBiologyT cellTranscriptomeFunction (biology)TransgeneAntigenMolecular biologyCancer researchGene expressionImmunologyImmune systemGeneIn vitroBiochemistryCAR-T cell therapy researchImmune Cell Function and InteractionT-cell and B-cell Immunology