PuSH - Publikationsserver des Helmholtz Zentrums München: IL-7-dependent compositional changes within the gamma delta T cell pool in lymph nodes during ageing lead to an unbalanced anti-tumour response.

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Chen, H.C.* ; Eling, N.* ; Martinez Jimenez, C.P. ; O'Brien, L.M.* ; Carbonaro, V.* ; Marioni, J.C.* ; Odom, D.T.* ; de la Roche, M.*

IL-7-dependent compositional changes within the gamma delta T cell pool in lymph nodes during ageing lead to an unbalanced anti-tumour response.

EMBO Rep. 20:e47379 (2019)

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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 gamma delta 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 gamma delta T cells, and gamma delta TCR diversity remains stable. However, ageing alters TCR delta chain usage and clonal structure of gamma delta T-cell subsets. Importantly, IL-17-producing gamma delta 17 T cells dominate the gamma delta T-cell pool of aged mice-mainly due to the selective expansion of V gamma 6(+) gamma delta 17 T cells and augmented gamma delta 17 polarisation of V gamma 4(+) T cells. Expansion of the gamma delta 17 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 V gamma 6(+) gamma delta 17 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 gamma delta T-cell pool in the pLN lead to an unbalanced gamma delta T-cell response in the tumour that is associated with accelerated tumour growth.

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