Optical control of CD8+ T cell functions at the tumour sites

2017-05-18 14:37:22 | 日記
To demonstrate the clinical implications of CatCh-mediated immune boosts, we examined the ability of CatCh to enhance the cytotoxicity of adoptively transferred tumour-specific CD8+ Tc and to improve antigen-specific tumour regression. In this study, we used the Pmel-1 TCR transgenic mouse model, a well characterized mouse tumour model for low-immunogenicity, which expresses the Vα1Vβ13 TCR that recognizes an H-2Db-restricted epitope corresponding to amino acids 25–33 of mouse gp100 (mgp100) on the B16 melanoma cells36. B16 melanoma cells grow at a normal rate in Pmel-1 mice despite the presence of overwhelming numbers of mgp100-specific CD8+ T cells36 (Fig. 4a). Furthermore, antigen-specific vaccination with a self-antigen, mgp100 or a mgp100 altered peptide ligand (for example, human gp100; hgp100) is not sufficient to improve the antitumour effects of adoptively transferred Pmel-1 T cells against B16 tumours due to an increase in the local CD4+FoxP3+ Treg cell population36,37. To determine whether the activation of adoptively transferred CD8+ Tc could be enhanced in order to treat established solid tumours, we first demonstrated that light stimulation of CatCh could deliver highly selective Ca2+ stimulation in Pmel-1 T cells and thus boost their effector functions under the Treg-mediated suppression. Light activation of CatCh-expressing Pmel-1 CD8+ Tc significantly increased killing of hgp10025–33 peptide (KVPRNQDWL)-loaded B16 target cells, allowing them to successfully overcome the Treg-mediated suppression
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