The promise of γδ T cells and the γδ T cell receptor for cancer immunotherapy

• Published in: Cellular & molecular immunology 2015-11, Vol.12 (6), p.656-668
• Main Authors: Legut, Mateusz, Cole, David K, Sewell, Andrew K
• Format: Article
• Language: English
• Subjects: Antibodies; Antigen Presentation; Antigens, CD1 - genetics; Antigens, CD1 - immunology; Antigens, Neoplasm - genetics; Antigens, Neoplasm - immunology; Biomedical and Life Sciences; Biomedicine; Clinical Trials as Topic; Gene Expression Regulation, Neoplastic - immunology; Hemiterpenes - immunology; Humans; Immunology; Immunotherapy - methods; Ligands; Medical Microbiology; Microbiology; Models, Molecular; Monitoring, Immunologic; Neoplasms - genetics; Neoplasms - immunology; Neoplasms - pathology; Neoplasms - therapy; Organophosphorus Compounds - immunology; Phosphorylation; Protein Structure, Tertiary; Receptors, Antigen, T-Cell, gamma-delta - genetics; Receptors, Antigen, T-Cell, gamma-delta - immunology; Review; Signal Transduction; T-Lymphocytes - immunology; T-Lymphocytes - pathology; T-Lymphocytes - transplantation; TCR; T细胞受体; Vaccine; γδT细胞; 免疫反应; 免疫治疗; 组成部分; 细胞识别; 肿瘤治疗
• ISSN: 1672-7681; 2042-0226
• DOI: 10.1038/cmi.2015.28

γδ T cells form an important part of adaptive immune responses against infections and malignant transformation. The molecular targets of humanγδT cell receptors （TCRs） remain largely unknown, but recent studies have confirmed the recognition of phosphorylated prenyl metabolites, lipids in complex with CD1 molecules and markers of cellular stress. All of these molecules are upregulated on various cancer types, highlighting the potential importance of the γδ T cell compartment in cancer immunosurveiliance and paving the way for the use of γδTCRs in cancer therapy. Ligand recognition by the γδ TCR often requires accessorylco-stimulatory stress molecules on both T cells and target cells; this cellular stress context therefore provides a failsafe against harmful self-reactivity. Unlike αβ T cells, γδ T cells recognise their targets irrespective of HLA haplotype and therefore offer exciting possibilities for off-the-shelf, pan-population cancer immunotherapies. Here, we present a review of known ligands of human γδ T cells and discuss the promise of harnessing these cells for cancer treatment.