IL‐7‐dependent compositional changes within the γδ T cell pool in lymph nodes during ageing lead to an unbalanced anti‐tumour response. (8th July 2019)

• Record Type: Journal Article
• Authors: Chen, Hung‐Chang; Eling, Nils; Martinez‐Jimenez, Celia Pilar; O'Brien, Louise McNeill; Carbonaro, Valentina; Marioni, John C; Odom, Duncan T; de la Roche, Maike
• Is Part Of: EMBO reports. Volume 20:Number 8(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-07-08
• Subjects: ageing -- IL‐7 -- lymph node -- tumour response -- γδ T‐cell lineage; Molecular biology -- Periodicals; Molecular Biology -- Periodicals; Molecular biology; Periodicals; 572.8
• DOI: 10.15252/embr.201847379
• Languages: English
• ISSNs: 1469-221X

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. Synopsis: Upon ageing, γδ17 T cells expand at the expense of γδ1 T cells in response to increased IL‐7 in the peripheral lymph nodes. This leads to enhanced infiltration of γδ17 T cells into the tumour microenvironment, promoting faster tumour growth. Ageing alters the composition of the γδ TCR repertoire in the peripheral lymph nodes (pLNs). IL‐7 expression is increased in the pLNs upon ageing and mediates the gradual expansion of γδ17 T cells. Expanded γδ17 T cells are activated in the tumour‐draining LN, and migrate into the tumour microenvironment. Abstract : Upon ageing, γδ17 T cells expand at the expense of γδ1 T cells in response to increased IL‐7 in the peripheral lymph nodes. This leads to enhanced infiltration of γδ17 T cells into the tumour microenvironment, promoting faster tumour growth.