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Human Tumor-Targeting Immune Cells Inhibited by the Protein BTLA

Dec. 28, 2009 — 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.


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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.

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The above story is reprinted from materials provided by Journal of Clinical Investigation, via EurekAlert!, a service of AAAS.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.


Journal References:

  1. Laurent Derré, 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
  2. 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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