Exploiting T cell signaling to optimize engineered T cell therapies.

Engineered T cell therapies, mainly chimeric antigen receptor (CAR)-T and T cell receptor (TCR)-T, have become the new frontier of cancer treatment. CAR-T and TCR-T therapies differ in many aspects, including cell persistence and toxicity, leading to different therapeutic outcomes. Both TCR and CAR recognize antigens and trigger T cell mediated antitumor response, but they have distinct molecular structures and signaling properties. TCR represents one of the most complex receptors, while CAR is a single-chain chimera integrating modules from multiple immune receptors. Understanding the mechanisms underlying the strengths and limitations of both systems can pave the way for the development of next-generation T cell therapy. This review synthesizes recent findings on TCR and CAR signaling and highlights the potential strategies of T cell engineering by signaling refinement.