T cells are the key immune system component involved in killing cancer. Tumors produce signals that turn off these T cells, partially by forcing them to progressively differentiate (mature) into a hypofunctional state known as exhaustion. Scientists from St. Jude Children’s Research Hospital comprehensively examined the transcription factors involved in T-cell differentiation states in cancer. They then used this information to enhance anticancer activity in preclinical models by promoting or blocking T-cell differentiation. The findings, which have implications for cancer immunotherapy, were published today in Nature.
T cells are used in adoptive cell therapy (ACT) to target and kill cancer cells. Among ACTs, chimeric antigen receptor (CAR) T cells have shown clinical efficacy in blood cancers but have not been as effective in solid tumors. This variance in efficacy is partly because tumors promote T-cell exhaustion, in which the cells are less effective at actively killing cancer. The scientists showed they could precisely interrupt the flow of the differentiation process, thereby enhancing antitumor efficacy.
T cells are the cornerstone of tumor immunotherapy, and we found a new way to reprogram T cells to make them more effective. We can push them towards a specialized state so that they can be more functional tumor-killing cells.”
Hongbo Chi, Ph.D., St. Jude Department of Immunology
Modifying differentiation to flow toward cancer-killing T cells
T-cell differentiation is conceptually similar to a river running down a mountain. The top of the mountain is the precursor cell, and the bottom an exhausted