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

Abstract

In mice, IFN{gamma}-producing {gamma}{delta} 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 {beta} T cells as well as homology with human {gamma}{delta} T cells is poorly understood. Here, using single cell RNA sequencing, we show that CD27+ {gamma}{delta} T cells consist of two major clusters, which are distinguished by expression of Ly6C. We demonstrate that CD27+Ly6C-- {gamma}{delta} T cells exhibit a naive T cell-like phenotype, whereas CD27+Ly6C+ {gamma}{delta} 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 {gamma}{delta} T cells. In a breast cancer mouse model, depletion of CD27+ {gamma}{delta} 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 {gamma}{delta} T cells in mice that are comparable to human {gamma}{delta} T cells, opening new opportunities for {gamma}{delta} T cell-based cancer immunotherapy research.