title: Direct Toll-Like Receptor 8 signaling increases the functional avidity of human CD8+ T lymphocytes generated for adoptive T cell therapy strategies.
abstract: Adoptive transfer of in vitro activated and expanded antigen-specific cytotoxic T lymphocytes (CTLs) is a promising therapeutic strategy for infectious diseases and cancers. Obtaining in vitro a sufficient amount of highly specific cytotoxic cells and capable of retaining cytotoxic activity in vivo remains problematic. We studied the role of Toll-Like Receptor-8 (TLR8) engagement on peripheral CTLs activated with melanoma antigen MART-1-expressing artificial antigen-presenting cells (AAPCs). After a 3-week co-culture, 3-27% of specific CTLs were consistently obtained. CTLs expressed TLR8 in the intracellular compartment and at the cell surface. Specific CTLs activated with a TLR8 agonist (CL075) 24 h before the end of the culture displayed neither any change in their production levels of molecules involved in cytotoxicity (IFN-γ, Granzyme B, and TNF-α) nor major significant change in their cell surface phenotype. However, these TLR8-stimulated lymphocytes displayed increased cytotoxic activity against specific peptide-pulsed target cells related to an increase in specific anti-melanoma CTL functional avidity. TLR8 engagement on CTLs could, therefore, be useful in different immunotherapy strategies.
authors: University of Rouen Rouen, France ; Institut National de la Santé et de la Recherche Médicale (INSERM) U905 Rouen, France.
authors: Jean-François
authors: JF
authors: Chatillon
authors: University of Rouen Rouen, France ; INSERM U1079 Rouen, France.
authors: Mohamad
authors: M
authors: Hamieh
authors: Institut National de la Santé et de la Recherche Médicale (INSERM) U905 Rouen, France.
authors: Florence
authors: F
authors: Bayeux
authors: University of Rouen Rouen, France ; Institut National de la Santé et de la Recherche Médicale (INSERM) U905 Rouen, France ; Rouen University Hospital Rouen, France.
authors: Claire
authors: C
authors: Abasq
authors: University of Rouen Rouen, France ; INSERM U1079 Rouen, France.
authors: Emilie
authors: E
authors: Fauquembergue
authors: INSERM U1079 Rouen, France.
authors: Aurélie
authors: A
authors: Drouet
authors: University of Rouen Rouen, France ; Institut National de la Santé et de la Recherche Médicale (INSERM) U905 Rouen, France ; Rouen University Hospital Rouen, France.
authors: Florian
authors: F
authors: Guisier
authors: University of Rouen Rouen, France ; INSERM U1079 Rouen, France ; Rouen University Hospital Rouen, France.
authors: Jean-Baptiste
authors: JB
authors: Latouche
authors: University of Rouen Rouen, France ; Institut National de la Santé et de la Recherche Médicale (INSERM) U905 Rouen, France ; Rouen University Hospital Rouen, France.
authors: Philippe
authors: P
authors: Musette
keywords: Toll-Like receptors; cytotoxic T lymphocytes; functional avidity; immunotherapy; melanoma