Issue |
Med Sci (Paris)
Volume 26, Number 2, Février 2010
|
|
---|---|---|
Page(s) | 185 - 192 | |
Section | M/S revues | |
DOI | https://doi.org/10.1051/medsci/2010262185 | |
Published online | 15 February 2010 |
Lymphocytes Tγδ en cancérologie
Des lymphocytes tueurs non conventionnels
Innate and adaptive killers: the gamma delta cells’ lifestyle
1
EE 341 Biothérapies innovantes, Université de Rennes 1, Faculté de Médecine de Rennes, 2, avenue du Pr. L. Bernard, Rennes Cedex 35043, France
2
Inserm U563, CPTP, CHU Purpan, 31000 Toulouse, France
*
veronique.catros@univ-rennes1.fr
Les lymphocytes Tγδ présentent à la fois des caractéristiques de cellules de l’immunité innée et de l’immunité adaptative. Ils expriment le récepteur de reconnaissance des antigènes TCR associé au complexe CD3 - mais sa diversité est moindre que celle du TCR des lymphocytes Tαβ - et n’expriment que rarement CD4 ou CD8. Chez l’homme, la sous-population majoritaire dans le sang est de type T Vγ9Vδ2. Les T Vγ9Vδ2 peuvent lyser les cellules tumorales en reconnaissant à leur surface de petits métabolites phosphorylés, les phosphoantigènes (PAg). Ces molécules et leurs analogues synthétiques (Phosphostim™) permettent de nouvelles stratégies thérapeutiques fondées sur les lymphocytes Tγδ, décrits dans cet article.
Abstract
Gamma delta T cells are a distinct subset of CD3+ T cells featuring both T cells receptors that are encoded by Vgamma- and Vdelta- gene segments and characteristics of innate immunity. In human blood, 80% of those express Vgamma9Vdelta2-TCRs that are specific for conserved non peptidic compound, phosphoantigens (PAgs). Vγ9Vδ2 T cells recognize in vitro a wide array of transformed cells and are activated in vivo in various tumor. Owing to their ability to directly kill tumor cells and produce inflammatory cytokines (such as IFN-γ) boosting antitumor properties of other immune effector cells, gamma delta T cells contribute to protective immunity against cancers. These observations, and the recent availability of synthetic clinical grade PAg or pharmacological inducers of PAg (e.g. aminobisphosphonates) able to trigger Vγ9Vδ2 T cell, have fostered development of new γδ T cell-based therapeutic strategies, which are depicted in this review.
© 2010 médecine/sciences - Inserm / SRMS
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