Both “killer” T cells and natural killer (NK) cells can eliminate tumor cells, but they can also both become “exhausted” within tumors via immune checkpoint pathways such as PD-1/PD-L1 and Tim-3 that limit their activity. Therefore, in order to figure out the most effect ways to reverse and/or prevent this exhaustion, Dr. Seo is focused on better understanding the mechanisms that enable it. His sponsor previously found that T cells with low functionality had similar gene expression profiles and were characterized by the activation of the Nr4a family of transcription factors that are responsible for the expression of certain genes. Additionally, she showed that T cells that lacked these Nr4a members experienced less exhaustion and exhibited increased activity similar to those treated with anti-PD-L1 checkpoint immunotherapy.
Now, Dr. Seo is comparing exhausted T cells with exhausted NK cells to identify the features they share. Specifically, he’s investigating the mechanistic roles of the Nr4a family members and determining if they’re also involved in NK cell exhaustion. Finally, he plans to extend these studies to human T and NK cells in both healthy people and cancer patients. Overall, he hopes that his work will provide additional clues about exhaustion in these cell types and reveal other potentially valuable targets for immunotherapy.
Projects and Grants
Analysis of NFAT and Nr4a mediated epigenetic reprogramming of tumor-infiltrating immune cell exhaustion
La Jolla Institute for Allergy and Immunology | All Cancers | 2019 | Anjana Rao, Ph.D.
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