Division of Infection and Immunity, Institute of Immunity and Transplantation, University College London, Royal Free Hospital, London NW3 2PF, UK.
Cancer Institute, Royal Free Hospital, University College London, London NW3 2PF, UK.
Cells. 2020 Jul 18;9(7):1721. doi: 10.3390/cells9071721.
This review presents key advances in combining T cell receptor (TCR) gene transfer to redirect T-cell specificity with gene engineering in order to enhance cancer-protective immune function. We discuss how emerging insights might be applied to CD4+ T cells. Although much attention has been paid to the role of CD8+ cytotoxic T cells in tumour protection, we provide convincing evidence that CD4+ helper T cells play a critical role in cancer immune responses in animal models and also in patients. We demonstrate that genetic engineering technologies provide exciting opportunities to extend the specificity range of CD4+ T cells from MHC class-II-presented epitopes to include peptides presented by MHC class I molecules. Functional enhancement of tumour immunity can improve the sensitivity of T cells to cancer antigens, promote survival in a hostile tumour microenvironment, boost cancer-protective effector mechanisms and enable the formation of T-cell memory. Engineered cancer-specific CD4+ T cells may contribute to protective immunity by a direct pathway involving cancer cell killing, and by an indirect pathway that boosts the function, persistence and memory formation of CD8+ T cells.
这篇综述介绍了将 T 细胞受体 (TCR) 基因转移与基因工程相结合，以重新定向 T 细胞特异性，从而增强癌症保护免疫功能的主要进展。我们讨论了如何将新出现的见解应用于 CD4+ T 细胞。尽管人们对 CD8+ 细胞毒性 T 细胞在肿瘤保护中的作用给予了极大关注，但我们提供了令人信服的证据表明，CD4+ 辅助 T 细胞在动物模型和患者的癌症免疫反应中发挥着关键作用。我们证明，基因工程技术为扩展 CD4+ T 细胞的特异性范围提供了令人兴奋的机会，从 MHC Ⅱ类呈递的表位扩展到包括 MHC Ⅰ类分子呈递的肽。肿瘤免疫功能的增强可以提高 T 细胞对癌症抗原的敏感性，促进在恶劣的肿瘤微环境中的存活，增强癌症保护效应机制，并使 T 细胞记忆形成。工程化的癌症特异性 CD4+ T 细胞可以通过直接途径（涉及癌细胞杀伤）和间接途径（增强 CD8+ T 细胞的功能、持久性和记忆形成）来促进保护性免疫。
