Harnessing stem cell-like memory T cells for adoptive cell transfer therapy of cancer

Abstract

Immunotherapies based on the adoptive transfer of naturally occurring or gene-engineered tumor-reactive T cells can result in durable complete responses in patients with metastatic cancers. Increasing findings from mouse studies and clinical trials indicate that intrinsic properties related to the differentiation state of the transferred T cells are crucial to the success of adoptive immunotherapies. There is now evidence that stem cell-like T cells with enhanced capacity for self-renewal and the ability to derive potent effector T cells might be used to improve persistence and long-term anti-tumor immunity. Here, we describe the molecular, metabolic and cellular aspects of T cell differentiation and their relevance to cancer immunotherapy. We also discuss current efforts and new approaches that might potentiate T cellbased immunotherapies through the modulation of T cell fate and differentiation.