IL‐7‐dependent compositional changes within the γδ T cell pool in lymph nodes during ageing lead to an unbalanced anti‐tumour response

Abstract

Abstract How the age‐associated decline of immune function leads to increased cancer incidence is poorly understood. Here, we have characterised the cellular composition of the γδ T‐cell pool in peripheral lymph nodes (pLNs) upon ageing. We find that ageing has minimal cell‐intrinsic effects on function and global gene expression of γδ T cells, and γδTCR diversity remains stable. However, ageing alters TCRδ chain usage and clonal structure of γδ T‐cell subsets. Importantly, IL‐17‐producing γδ17 T cells dominate 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 is mediated by increased IL‐7 expression in the T‐cell zone of old mice. In a Lewis lung cancer model, pro‐tumourigenic Vγ6 + γδ17 T cells are exclusively activated in the tumour‐draining LN and their infiltration into the tumour correlates with increased tumour size in aged mice. Thus, upon ageing, substantial compositional changes in γδ T‐cell pool in the pLN lead to an unbalanced γδ T‐cell response in the tumour that is associated with accelerated tumour growth.