Heterogeneous yet stable Vδ2 ⁽⁺⁾ T-cell profiles define distinct cytotoxic effector potentials in healthy human individuals

Abstract

Significance A type of human white blood cell, known as the Vδ2 (+) T cell, has shown promise in immunotherapies against a range of tumors. However, in recent clinical trials patient responses and clinical outcomes have been variable and unpredictable. To address this, we here reveal a significant variability in Vδ2 (+) T-cell functional potential between individuals in the general population, which develops shortly after birth, is stable over time, and is manifested by differential mechanistic capacities to kill tumor targets. These results support personalized clinical approaches to identify patients with “Vδ2 profiles” that are compatible with killing of their particular tumor and suggest that tailored Vδ2-profile–specific activation protocols may maximize the chances of future treatment success.