Researchers Identify Heterogeneity of Tissue Resident Memory T Cells as Targets of Checkpoint Therapies

Researchers at Yale Cancer Center and Yale Medicine have identified the critical target of new immune-checkpoint therapies: subsets of immune cells called tissue resident memory (TRM) T cells. In the same research, scientists also found that individual metastatic cancer lesions contain unique sets of TRM cells.

The results of the study are published in the December 22 issue of the Journal of Clinical Investigation Insights.

“Immune checkpoint therapies have begun to transform cancer therapy,” said the study’s senior author, Kavita M. Dhodapkar, MD, Associate Professor of Pediatrics at Yale School of Medicine and Director of the Phase I Program in Pediatric Oncology at Smilow Cancer Hospital. “This research shows that the specific immune subset expressing these inhibitory molecules is a distinct subset called tissue resident memory T cells.”

Tumor tissue resident memory T cells are different from T cells circulating in the blood, both at a phenotypic and genomic level. “Each cancer lesion appears to carry a distinct set of these immune cells, meaning that the mechanism by which these immune therapies work (or fail) may differ in each of the lesions,” Dr. Dhodapkar said.

“We believe that ability to generate T cells with characteristics of TRM T cells will be important in allowing tumor-specific T cells to hone to and persist within tumors,” said Dr. Dhodapkar. “Understanding the biology of TRM cells and the factors that control the persistence of these T cells within tumors will allow us to improve upon the current immune therapies.”

Additional study authors include Chandra Boddupalli, Noffar Bar, Krishna Kadaveru, Michael Krauthammer, Natopol Pornputtapong, Zifeng Mai, Stephan Ariyan, Deepak Narayan, Harriet Kluger, Yanhong Deng, Rakesh Verma, Rituparna Das, Antonella Bacchiocchi, Ruth Halaban, Mario Sznol, and Madhav Dhodapkar.