Engineering CD4+ T Cells to Enhance Cancer Immunity

• Main Authors: Francesca Sillito, Angelika Holler, Hans J. Stauss
• Format: Article
• Language: English
• Published: MDPI AG 2020-07-01
• Series: Cells
• Subjects: T cell receptor (TCR); T helper cell (Th); major histocompatibility complex (MHC); mechanistic target of Rapamycin 1 (mTORC1); programmed death receptor 1 (PD-1); interferon-gamma (IFN-γ)
• Online Access: https://www.mdpi.com/2073-4409/9/7/1721

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.