Immune cells known as CD8+ T cells have important roles in protection against infectious diseases and cancer. Now, Daniel Speiser and colleagues, at the Ludwig Institute for Cancer Research, Switzerland, have determined that human CD8+ T cells that target tumors express much higher levels of an inhibitory molecule known as BTLA than human CD8+ T cells that target viruses.
The research appears in the Journal of Clinical Investigation.
Triggering of BTLA on these cells impaired their function. Further, persistently high levels of BTLA expression were detected on tumor-specific CD8+ T cells from melanoma patients who mounted spontaneous antitumor immune responses and after conventional peptide vaccination. More importantly, treating melanoma patients with both conventional peptide vaccination and a compound that decreased BTLA expression on tumor-specific CD8+ T cells restored the ex vivo functionality of the T cells.
The authors and, in an accompanying commentary, Chrystal Paulos and Carl June therefore suggest that it might be useful to combine approaches to inhibit BTLA-mediated T cell inhibition with conventional cancer vaccination strategies.
- Laurent Derrι, Jean-Paul Rivals, Camilla Jandus, Sonia Pastor, Donata Rimoldi, Pedro Romero, Olivier Michielin, Daniel Olive and Daniel E. Speiser. BTLA mediates inhibition of human tumor-specific CD8 T cells that can be partially reversed by vaccination. Journal of Clinical Investigation, Published December 28, 2009 DOI: 10.1172/JCI40070
- Chrystal M. Paulos and Carl H. June. Putting the brakes on BTLA in T cell-mediated cancer immunotherapy. Journal of Clinical Investigation, 2010;120(1):76%u201380 DOI: 10.1172/JCI41811
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