T cell-based cancer immunotherapy: opportunities and challenges

Abstract

T cells play a central role in the cancer immunity cycle. The therapeutic outcomes of T cell-based intervention strategies are determined by multiple factors at various stages of the cycle. Here, we summarize and discuss recent advances in T cell immunotherapy and potential barriers to it within the framework of the cancer immunity cycle, including T-cell recognition of tumor antigens for activation, T cell trafficking and infiltration into tumors, and killing of target cells. Moreover, we discuss the key factors influencing T cell differentiation and functionality, including TCR stimulation, costimulatory signals, cytokines, metabolic reprogramming, and mechanistic forces. We also highlight the key transcription factors dictating T cell differentiation and discuss how metabolic circuits and specific metabolites shape the epigenetic program of tumor-infiltrating T cells. We conclude that a better understanding of T cell fate decision will help design novel strategies to overcome the barriers to effective cancer immunity.

Keywords: CD8(+) T cell; Cancer immunotherapy; Differentiation; Epigenetic regulation; Metabolism.