Department of Dermatology, University of Zurich, Zurich, Switzerland.
Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland.
Front Immunol. 2019 Jul 5;10:1548. doi: 10.3389/fimmu.2019.01548. eCollection 2019.
Cytotoxic T lymphocytes (CTLs) are key players in fighting cancer, and their induction is a major focus in the design of therapeutic vaccines. Yet, therapeutic vaccine efficacy is limited, in part due to the suboptimal vaccine processing by antigen-presenting cells (APCs). Such processing typically takes place via the MHC class II pathway for CD4 T-cell activation and MHC class I pathway for activation of CD8 CTLs. We show that a combination of skin photochemical treatment and immunization, so-called photochemical internalization (PCI) facilitated CTL activation due to the photochemical adjuvant effect induced by photosensitizer, oxygen, and light. Mice were immunized intradermally with antigen and photosensitizer, followed by controlled light exposure. PCI-treated mice showed strong activation of CD8 T cells, with improved IFN-γ production and cytotoxicity, as compared to mice immunized without parallel PCI treatment. Surprisingly, the CD8 T-cell effector functions were not impaired in MHC class II- or CD4 T-cell-deficient mice. Moreover, PCI-based vaccination caused tumor regression independent of MHC class II or CD4 T cells presence in melanoma bearing mice. Together, the data demonstrate that PCI can act as a powerful adjuvant in cancer vaccines, even in hosts with impaired T-helper functions.
细胞毒性 T 淋巴细胞（CTLs）是抗癌的关键因素，其诱导是治疗性疫苗设计的主要焦点。然而，治疗性疫苗的疗效有限，部分原因是抗原呈递细胞（APCs）对疫苗的处理不理想。这种处理通常通过 MHC 类 II 途径进行 CD4 T 细胞的激活，通过 MHC 类 I 途径进行 CD8 CTL 的激活。我们表明，皮肤光化学处理和免疫接种的组合，即所谓的光化学内化（PCI），由于光增敏剂、氧气和光诱导的光化学佐剂效应，促进了 CTL 的激活。用抗原和光增敏剂对小鼠进行皮内免疫，然后进行受控的光暴露。与未经平行 PCI 处理的免疫小鼠相比，PCI 处理的小鼠表现出强烈的 CD8 T 细胞激活，IFN-γ产生和细胞毒性得到改善。令人惊讶的是，在 MHC 类 II 或 CD4 T 细胞缺陷型小鼠中，CD8 T 细胞的效应功能并未受损。此外，基于 PCI 的疫苗接种可导致肿瘤消退，而与黑色素瘤荷瘤小鼠中 MHC 类 II 或 CD4 T 细胞的存在无关。总之，这些数据表明，即使在 T 辅助功能受损的宿主中，PCI 也可以作为癌症疫苗的强大佐剂。
