Table 1. γδ T cells offer escape from issues limiting αβ T cell-based immunotherapies.

Phenotype relevant to immunotherapies	αβ T cells	γδ T cells
MHC-restriction limits unrestricted clinical application	Yes, for most αβ T cells	No obligate MHC restriction for γδ T cells
Resistant to cancer cell loss of β2-microglobulin	No	Yes (function may be enhanced by this status) Yes: no evidence for widespread GVHD
Function as allogeneic therapy off-the-shelf (a)	No: drives graft-versus-host disease (GVDH)
Function as allogeneic therapy off-the-shelf (b)	No: requires "cloaking" to avoid rejection	No: requires "cloaking" to avoid rejection; may also veto rejection
Home to and function within extralymphoid tissues	Some subsets (e.g., TRM) adapt to tissues	Many subsets naturally localize to and function within tissues
Readily recognise tumors with low neoantigen load	Only unconventional subsets (NKT, MAIT) may do this	Yes
Recognise a potentially vast diversity of cancer surface antigens	No	Yes
Responds to ICB	Yes	Yes, with PD-1+ non-Vδ2 cells showing less exhaustion than PD1+ CD8+ αβ T cells
Mostly cytolytic	No	Yes
Adverse events	Potentially high because of CRS and cross-reactivity to normal self	Limited CRS because small fraction of CD3+ cells, and because of natural therapeutic window
Establishing cure via immunological memory	Yes, directly	Yes, with capacity to orchestrate CD8+ αβ T cell memory
ADCC	No, unless CAR-T engineered	Yes, naturally
Capacity to cross-present peptide antigens to αβ T cells	No	Yes for Vγ9Vδ2 T cells