Investigating the contribution of gamma-delta T-cells to immunosurveillance of cancer and response to immunotherapy

Modifying the immune system, particularly T-cells, can now cure some patients with stage-4 cancer. However, most patients do not benefit. T-cells are white blood cells which can be further divided into alpha-beta and gamma-delta T-cells. Most current therapies work on alpha-beta T-cells. Gamma-delta T-cells can control cancers in mice, but remain under-utilised in human therapy as clinical trials involving these cells have been disappointing. Using modern sequencing and cell-growing technologies previously not widely available, we recently demonstrated that only certain gamma-delta T-cells, the V-delta-1 subtype, predict survival in aggressive breast cancers. Here we will extend the characterisation of these cells, in far greater detail, into a pan-cancer setting to include melanoma, lung, breast and other cancers. By defining what makes these V-delta-1 cells protective, we will instruct ongoing and future gamma-delta T-cell therapy trials and thus open up effective immunotherapy to those who do not benefit from alpha-beta T-cell therapies.