Benjamin A. Youngblood, PhD, assistant member, Department of Immunology, St. Jude Children’s Research Hospital, discusses the process of T-cell differentiation in pediatric solid tumors.

Youngblood, an epigenetic specialist, says he works regularly with clinicians to look at donated solid tumor samples. The biggest aspect of analysis is to figure out why the T cells aren’t functioning properly. The microenvironment of the cells is also important, as well as determining if the T cells are interacting outside the tumor itself. This all impacts the cells’ endogenous response.

Youngblood says he is working with Stephen Gottschalk, MD, at St. Jude Children’s Research Hospital to characterize the differentiation in chimeric antigen receptor (CAR) T cells. This process involves looking at functional cell responses and defining these at an epigenetic level. With this information, Youngblood says, researchers can decide what the CAR T cells should look like compared with how their samples look. This could eventually be applied to targeted therapy in pediatric solid tumors.

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Dr. Youngblood on the Process of T-Cell Differentiation in Pediatric Solid Tumors

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.”

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.

Benjamin A. Youngblood, PhD

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Dr. Youngblood on the Process of T-Cell Differentiation in Pediatric Solid Tumors

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