Effective γδ T-cell clinical therapies: current limitations and future perspectives for cancer immunotherapy.

γδ T cells are a unique subset of T lymphocytes, exhibiting features of both innate and adaptive immune cells and are involved with cancer immunosurveillance. They present an attractive alternative to conventional T cell-based immunotherapy due, in large part, to their lack of major histocompatibility (MHC) restriction and ability to secrete high levels of cytokines with well-known anti-tumour functions. To date, clinical trials using γδ T cell-based immunotherapy for a range of haematological and solid cancers have yielded limited success compared with in vitro studies. This inability to translate the efficacy of γδ T-cell therapies from preclinical to clinical trials is attributed to a combination of several factors, e.g. γδ T-cell agonists that are commonly used to stimulate populations of these cells have limited cellular uptake yet rely on intracellular mechanisms; administered γδ T cells display low levels of tumour-infiltration; and there is a gap in the understanding of γδ T-cell inhibitory receptors. This review explores the discrepancy between γδ T-cell clinical and preclinical performance and offers viable avenues to overcome these obstacles. Using more direct γδ T-cell agonists, encapsulating these agonists into lipid nanocarriers to improve their pharmacokinetic and pharmacodynamic profiles and the use of combination therapies to overcome checkpoint inhibition and T-cell exhaustion are ways to bridge the gap between preclinical and clinical success. Given the ability to overcome these limitations, the development of a more targeted γδ T-cell agonist-checkpoint blockade combination therapy has the potential for success in clinical trials which has to date remained elusive.

Metal ion sensing with graphene quantum dots: detection of harmful contaminants and biorelevant species.

Graphene quantum dots (GQDs) are attractive materials for use as highly selective and sensitive chemical sensors, owing to their simple preparation and affordability. GQDs have been successfully deployed as sensors for toxic metal ions, which is a significant issue due to the ever-increasing environmental contamination from agricultural and industrial activities. Despite the success of GQDs in this area, the mechanisms which underpin GQD-metal ion specificity are rarely explored. This lack of information can result in difficulties when attempting to replicate published procedures and can limit the judicious design of new highly selective GQD sensors. Furthermore, there is a dearth of GQD examples which selectively detect biologically relevant alkali and alkaline earth metals. This review will present the current state of GQDs as metal ion sensors for harmful contaminants, highlighting and discussing the discrepancies that exist in the proposed mechanisms regarding metal ion selectivity. The emerging field of GQD sensors for biorelevant metal ion species will also be reviewed, with a perspective to the future of this highly versatile material.