Dr. Youngblood on T-Cell Differentiation/Exhaustion in Pediatric Cancer

Benjamin A. Youngblood, PhD, assistant member, Department of Immunology, St. Jude Children’s Research Hospital, discusses the impact of T-cell differentiation and exhaustion in pediatric cancer. He highlighted how epigenetic regulation of T cells can relate to patient response to immunotherapy.

In designing a chimeric antigen receptor T-cell product, Youngblood says, a common problem that experts come across is that these cells still become exhausted, as they’ve defined a mechanism for exhaustion. A potential solution is that if researchers can identify the enzyme causing this, they can engineer a T cell from the start and make it resistant, instead of acquiring these exhaustion profiles. An alternative could be to reprogram the host endogenous T cells. A widespread assumption in dealing with pediatric tumors is that response is low because tumor mutation burden is low. Youngblood says this isn’t the case and that endogenous response is always there.

He adds that readily available drugs can be used to “walk cells back down the differentiation pathway.”