How age-associated decline of immune function leads to increased cancer incidence is poorly understood. Here, we have characterized the cellular composition of the γδ T cell pool in peripheral lymph nodes (pLNs) upon ageing. We found that ageing has minimal cell-intrinsic effects on function and global gene expression of γδ T cells, and TCRγδ diversity remained stable. However, ageing altered TCRδ chain usage and clonal structure of γδ T cell subsets. Importantly, IL-17-producing γδ17 T cells dominated the γδ T cell pool of aged mice - mainly due to the selective expansion of Vγ6+ γδ17 T cells and augmented γδ17-polarisation of Vγ4+ T cells. Expansion of the γδ17 T cell compartment was supported by increased Interleukin-7 expression in the T cell zone of old mice. In a Lewis lung cancer model, pro-tumourigenic Vγ6+ γδ17 T cells were exclusively activated in the tumour-draining LN and their infiltration into the tumour correlated with increased tumour size in aged mice. Thus, upon ageing, substantial compositional changes of γδ T cell pool in a dysregulated pLN microenvironment promote tumour growth.

Altered composition of the γδ T cell pool in lymph nodes during ageing enhances tumour growth