Researchers from The Scripps Research Institute and the University of California, San Diego report that a protein called Runx3 programs killer T cells to establish residence in tumors and infection sites. The work will appear later this week in Nature's Thursday issue.
One main strategy in cancer immunotherapy is called adoptive cell transfer. This involves re-infusing a patient's own immune cells after they have been engineered in the lab to recognize and destroy the patient's specific cancer. Adoptive cell transfer has been found to work well in some blood cancer, but not as efficient in solid tumors.
To discover factors that control T cell residency beyond the lymphoid system, Ananda Goldrath's lab at UC San Diego compared the gene expression of CD8+ T cells found in non-lymphoid tissue to those found in the general circulation. From a list of potential factors, they employed an RNA interference screening strategy to test the actual function of thousands of factors simultaneously.
"We found a distinct pattern," said Matthew Pipkin, associate professor at The Scripps Research Institute. "The screens showed that Runx3 is one at the top of a list of regulators essential for T cells to reside in nonlymphoid tissues." He also notes that Runx3 was capable of engaging a specific gene program that is found in natural tissue-resident and tumor-infiltrating CD8+ T cells.
The group looked into more detail on Runx3's role using mouse models and found that adoptive cell transfer of cancer-specific killer T cells that overexpressed Runx3 delayed tumor growth and prolonged survival. The mouse models that that lacked Runx3 experienced much worse outcomes than normal mice.
"If we enhance Runx3 activity in the cells, the tumors are significantly smaller and there is greater survival compared to the control group," Pipkin said.
With the new findings on Runx3, there could be potential in improving solid tumor cancer immunotherapies.