Ly6C defines a subset of memory-like CD27+ γδ T cells with inducible cancer-killing function

In mice, IFNγ-producing γδ T cells that express the co-stimulatory molecule, CD27, play a critical role in host defence and anti-tumour immunity. However, their phenotypic diversity, composition in peripheral and secondary lymphoid organs, similarity to αβ T cells as well as homology with human γδ T cells is poorly understood. Here, using single cell RNA sequencing, we show that CD27+ γδ T cells consist of two major clusters, which are distinguished by expression of Ly6C. We demonstrate that CD27+Ly6C— γδ T cells exhibit a naïve T cell-like phenotype, whereas CD27+Ly6C+ γδ T cells display a memory-like phenotype, produce several NK cell-related and cytotoxic molecules and are highly similar to both mouse CD8+ T cells and mature human γδ T cells. In a breast cancer mouse model, depletion of CD27+ γδ T cells failed to affect tumour growth, but these cells could be coerced into killing cancer cells after expansion ex vivo. These results identify novel subsets of γδ T cells in mice that are comparable to human γδ T cells, opening new opportunities for γδ T cell-based cancer immunotherapy research.