Research Seeks to Weaponize T Cells in Attacking Tumors

Enzyme acts as an epigenetic checkpoint of T cell function to treat cancer.

The histone deacetylase 11 (HDAC11) enzyme acts as an epigenetic checkpoint of T cell function in the treatment of cancer tumors, new research shows.

For a study published in Blood, investigators sought to gain a better understanding of the underlying mechanisms of T cell function and epigenetic regulation of the HDAC11 enzyme.

Although T cells are known to infiltrate tumors and attack the cancerous cells, prior studies show that the group of T cells surrounding the tumor do not perform the job they are supposed to.

“The goal of the T cell is to destroy the cancer cells,” said senior author Eduardo M. Sotomayor, MD. “We wanted to look at and understand the mechanisms that allowed crosstalk between the tumor and the T cells that stopped the T cells from doing their job.”

The investigators focused on the discovery of epigenetic checkpoints in T cell function to help explain how and why these cells are modified to act differently. The results of the study showed that when HDAC11 enzymes were removed from the T cells, they were more primed to attack the tumor.

The findings highlight that HDAC11 should be treated as an immunotherapeutic target, the authors noted.

“We don’t want T cells to be easily activated, as they can cause harm to the hose—–the patient,” Sotomayor said. “So we want to look at possible methods and therapies to activate the T cells when they need to work.”

The investigators plan to continue their research and aim to improve the T cells ability to attack and kill cancer tumors.

“The next step is to perform preclinical studies with specific inhibitors of HDAC11 alone and in tandem with other existing immunotherapies, such as anti-PD1/anti-PDL1 antibodies, in order to find the most potent combination,” Sotomayor said. “Our goal is to make the T cells better at destroying cancer tumors.”