New insights into tumor-infiltrating T cells
- Date:
- September 8, 2016
- Source:
- Brigham and Women's Hospital
- Summary:
- A distinct gene module for T cell dysfunction distinct from activation in tumor-infiltrating T cells has now been discovered, thus paving the way for the development of new precision therapeutics.
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Investigators from Brigham and Women's Hospital have identified a distinct gene module for T cell dysfunction distinct from activation in tumor-infiltrating T cells, thus paving the way for the development of new precision therapeutics.
T cell dysfunction (also called exhaustion) arises in chronic disease states such as cancer and chronic viral infections. New treatments that aim to reverse T cell dysfunction, such as checkpoint inhibitors, have been very effective, but only for certain patients and certain tumor types. To better understand the molecular underpinnings of T cell dysfunction, the research team analyzed tumor-infiltrating lymphocytes (TILs), using single-cell as well as cell-population analysis techniques. They identified several pathways as well as a transcription factor, Gata-3, that contribute to T cell dysfunction, and used CRISPR/Cas9 genome editing to further demonstrate the role of Gata-3 in T cell dysfunction.
"Our work opens up new avenues for specifically targeting the dysfunctional T cell state while leaving the programs that drive T cell activation intact," said Ana C. Anderson, PhD, an associate scientist at BWH.
Story Source:
Materials provided by Brigham and Women's Hospital. Note: Content may be edited for style and length.
Journal Reference:
- Singer M et al. A Distinct Gene Module for Dysfunction Uncoupled from Activation in Tumor-Infiltrating T Cells. Cell, September 2016 DOI: 10.1016/j.cell.2016.08.052
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