Barisa, M; Fowler, D; Fisher, J; (2021) Interplay between γδT-Cell Metabolism and Tumour Microenvironment Offers Opportunities for Therapeutic Intervention. Immunometabolism , 3 (3) , Article e210026. 10.20900/immunometab20210026.

Preview

Text Barisa_IJ_1417.pdf - Published Version Download (1MB) | Preview

Abstract

Solid tumour targeting using adoptive cell therapy has failed to reproduce the spectacular clinical successes seen with chimeric antigen receptor T cell therapies and B cell malignancies. Low in glucose, oxygen, pH and populated with suppressive cells, the solid tumour microenvironment (TME) remains a formidable obstacle to successful immune targeting. The use of atypical, tissue-tropic lymphocytes, such as γδT cells, may offer enhanced tumour trafficking over canonical αβT cells. Nonetheless, γδT cells too interact with the TME. The consequences of this interaction are poorly understood and of high translational relevance. Lopes and colleagues show that, in a murine context, low glucose environments preferentially retained pro-tumorigenic IL-17-producing γδT cells. Anti-tumorigenic IFN-γ-producing γδT cells, meanwhile, required high ambient glucose to survive and exert effector function. Unexpectedly, this metabolic imprinting was evident in the murine thymus, suggesting that the ontological separation of these functional subsets occurs early in their development. Elucidation of this relationship between TME glucose levels and γδT cell functionality in a human context is likely to carry significant implications for the development of γδT cell-based oncoimmunotherapeutics.

Download activity - last month

Export as JSONCSVXML

Download activity - last 12 months

Export as CSVXMLJSON

Downloads by country - last 12 months

Export as JSONXMLCSV

Archive Staff Only

View Item