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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.
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https://hal-normandie-univ.archives-ouvertes.fr/hal-02379928
Contributor : Jean-Baptiste Latouche <>
Submitted on : Monday, November 25, 2019 - 11:07:52 PM
Last modification on : Tuesday, October 20, 2020 - 10:17:36 AM

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Jean-François Chatillon, Mohamad Hamieh, Florence Bayeux, Claire Abasq, Emilie Fauquembergue, et al.. Direct Toll-Like Receptor 8 signaling increases the functional avidity of human CD8+ T lymphocytes generated for adoptive T cell therapy strategies. Immunity, Inflammation and Disease, John Wiley & Sons Ltd, 2015, 3 (1), pp.1-13. ⟨10.1002/iid3.43⟩. ⟨hal-02379928⟩

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