Turning Harmless Cells Into Ruthless Tumor and Virus Killers

Processes in the human body transform harmless immune cells into ruthless killers

A new study found that the human body has the power to transform typically innocuous immune cell clusters into merciless assassins capable of attacking tumor cells and other cells containing viruses or parasites.

Previously, it was thought that gamma delta T cells were "pre-programmed" to find and remove other rogue cells, but it now seems that some kinds of the cells share many similarities with well-known "adaptive" subsets of conventional T cells.

An multinational team of scientists from the United Kingdom, Australia, China, the Netherlands, and the United States—led by the University of Birmingham — noted significant resemblance to typical adaptive "killer" T cells in a recent paper in Cell Reports.

"Human gamma delta T cells have typically been assumed to be pre-programmed, however, our study shows that at least in blood, some types mirror the behavior of conventional T cells – suggesting they can be ‘trained’ to become extremely potent killers once they recognize aberrant target cells – including those infected with viruses, parasites, or possibly tumor cells."

"Our discovery has implications for efforts to develop gamma delta T cells as novel cellular therapies. We hope that it will change the way scientists think about these cells and how they might contribute to the treatment of cancer and infectious disease."

The study, funded in part by a Wellcome Trust Investigator Award, looked at the gene expression profile of human gamma delta T cells, revealing the cells in a far more 'adaptive' light.

In vertebrates, gamma delta cells coexist with alpha beta T cells and B cells. Researchers discovered that certain human gamma delta T cells appear to change their gene expression pattern to activate a 'killer' program when exposed to abnormal target cells, with successful recognition of such targets likely being a key factor in triggering this transformation and subsequent attack.

The striking similarity between gamma delta T cells and conventional adaptive killer T cells suggests that the unique contribution of gamma delta T cells is not the type of response they eventually mount - such as killing a target cell - but the ability to recognize abnormal target cells in a very different way.

This implies that they can mount unconventional adaptation responses when traditional adaptive T cells are unable to.

"Our research provides a basis for ongoing studies to understand how such unconventional adaptive gamma delta T cell responses are triggered, and also for efforts to harness such responses to develop new and more effective treatments for infections and cancer."

Reference: “Transcriptional profiling of human Vδ1 T cells reveals a pathogen-driven adaptive differentiation program” by Jack L. McMurray, Anouk von Borstel, Taher E. Taher, Eleni Syrimi, Graham S. Taylor, Maria Sharif, Jamie Rossjohn, Ester B.M. Remmerswaal, Frederike J. Bemelman, Felipe A. Vieira Braga, Xi Chen, Sarah A. Teichmann, Fiyaz Mohammed, Andrea A. Berry, Kirsten E. Lyke, Kim C. Williamson, Michael J.T. Stubbington, Martin S. Davey and Carrie R. Willcox, 24 May 2022, Cell Reports

DOI: 10.1016/j.celrep.2022.110858