Vaccination-induced skin-resident memory CD8+ T cells mediate strong protection against cutaneous melanoma
Vaccination-induced skin-resident memory CD8+ T cells mediate strong protection against cutaneous melanoma
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DOI：
10.1080/2162402x.2018.1442163
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发表时间：
2018-01-01
期刊：
影响因子：
7.2
通讯作者：
Lladser, Alvaro
中科院分区：
文献类型：
--
作者：
Galvez-Cancino, Felipe;Lopez, Ernesto;Lladser, Alvaro
记忆性CD8（+）T细胞应答有可能介导对癌症的持久保护。驻留记忆CD8（+）T（Trm）细胞稳定地驻留在非淋巴组织中，并介导针对病原体的上级先天性和适应性免疫。新出现的证据表明，Trm细胞在人类实体癌中发育，并在控制肿瘤生长中发挥关键作用。然而，Trm细胞对抗肿瘤免疫的具体贡献尚不完全清楚。此外，有效建立Trm细胞应答的临床上适用的疫苗接种策略在很大程度上仍未开发，并且预计将强烈保护免受肿瘤的侵害。在这里，我们证明了基于基因或蛋白质的疫苗的单次皮内施用有效地诱导针对肿瘤特异性和自身抗原模型的特异性Trm细胞应答，所述肿瘤特异性和自身抗原在接种疫苗和远处未接种疫苗的皮肤中积累。疫苗诱导的Trm细胞在很大程度上抵抗体内血管内染色和抗体依赖性耗竭。皮内，但不是腹膜内接种，产生的记忆前体表达皮肤归巢分子在循环和Trm细胞在皮肤中。有趣的是，疫苗诱导的Trm细胞反应强烈抑制B16 F10黑色素瘤的生长，独立于循环记忆CD8（+）T细胞，并能够浸润肿瘤。这项工作突出了疫苗诱导的Trm细胞反应的治疗潜力，以实现对皮肤恶性肿瘤的有效保护。
Memory CD8(+) T cell responses have the potential to mediate long-lasting protection against cancers. Resident memory CD8(+) T (Trm) cells stably reside in non-lymphoid tissues and mediate superior innate and adaptive immunity against pathogens. Emerging evidence indicates that Trm cells develop in human solid cancers and play a key role in controlling tumor growth. However, the specific contribution of Trm cells to anti-tumor immunity is incompletely understood. Moreover, clinically applicable vaccination strategies that efficiently establish Trm cell responses remain largely unexplored and are expected to strongly protect against tumors. Here we demonstrated that a single intradermal administration of gene- or protein-based vaccines efficiently induces specific Trm cell responses against models of tumor-specific and self-antigens, which accumulated in vaccinated and distant non-vaccinated skin. Vaccination-induced Trm cells were largely resistant to in vivo intravascular staining and antibody-dependent depletion. Intradermal, but not intraperitoneal vaccination, generated memory precursors expressing skin-homing molecules in circulation and Trm cells in skin. Interestingly, vaccination-induced Trm cell responses strongly suppressed the growth of B16F10 melanoma, independently of circulating memory CD8(+) T cells, and were able to infiltrate tumors. This work highlights the therapeutic potential of vaccination-induced Trm cell responses to achieve potent protection against skin malignancies.