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BTLA marks a less-differentiated tumor-infiltrating lymphocyte subset in melanoma with enhanced survival properties.
- Source :
-
OncoImmunology . Aug2015, Vol. 4 Issue 8, p00-00. 0p. - Publication Year :
- 2015
-
Abstract
- In a recent adoptive cell therapy (ACT) clinical trial using autologous tumor-infiltrating lymphocytes (TILs) in patients with metastatic melanoma, we found an association between CD8+T cells expressing the inhibitory receptor B- and T-lymphocyte attenuator (BTLA) and clinical response. Here, we further characterized this CD8+BTLA+TIL subset and their CD8+BTLA−counterparts. We found that the CD8+BTLA+TILs had an increased response to IL-2, were less-differentiated effector-memory (TEM) cells, and persisted longerin vivoafter infusion. In contrast, CD8+BTLA−TILs failed to proliferate and expressed genes associated with T-cell deletion/tolerance. Paradoxically, activation of BTLA signaling by its ligand, herpes virus entry mediator (HVEM), inhibited T-cell division and cytokine production, but also activated the Akt/PKB pathway thus protecting CD8+BTLA+TILs from apoptosis. Our results point to a new role of BTLA as a useful T-cell differentiation marker in ACT and a dual signaling molecule that curtails T-cell activation while also conferring a survival advantage for CD8+T cells. These attributes may explain our previous observation that BTLA expression on CD8+TILs correlates with clinical response to adoptive T-cell therapy in metastatic melanoma. [ABSTRACT FROM PUBLISHER]
Details
- Language :
- English
- ISSN :
- 21624011
- Volume :
- 4
- Issue :
- 8
- Database :
- Academic Search Index
- Journal :
- OncoImmunology
- Publication Type :
- Academic Journal
- Accession number :
- 109173551
- Full Text :
- https://doi.org/10.1080/2162402X.2015.1014246