Ageing and the anti-tumour response

New research from the de la Roche, Odom, and Marioni groups, has identified a novel age-dependent immune cell mechanism that enhances tumour growth.

Age is the single biggest risk factor for cancer, with over half of cancer cases occurring in people over the age of 70.¹ A long held tenet is that cancer risk is due to the build-up of mutations in our genomes. However, it is still poorly understood whether the decline of our anti-cancer immune functions with age also plays a prominent role.

New research from Hung-Chang Chen in the de la Roche Group, published today in EMBO Reports, focuses on the γδ T cells, a unique lymphocyte population that combines adaptive immune features with rapid innate-like functions for a robust, front line immune response to infection, tissue damage and cancer.  Unlike αβ T cells, which make up the majority of the T cell population, the identity of γδ T cells is specified in the thymus.

γδ T cells come in two flavours, an IFN-γ-producing subset with potent cytotoxic function against cancer and an IL-17-producing subset that is tumour promoting – encouraging angiogenesis and the recruitment of immune-suppressing cell types.

I’m very excited to have uncovered a novel role of these cells in specifying the local tumour microenvironment.

Dr Hung-Chang Chen, Cancer Research UK Cambridge Institute

So far, it has not been known how the γδ T cell population in the lymph node changes with ageing and how these changes may affect the tumour microenvironment.

The team has characterised the γδ T cell repertoire in the lymph node during ageing and how this affects the anti-tumour immune response.

They found that upon ageing, the pool of γδ T cells in lymph node becomes entirely biased towards the IL-17-producing lineage, and the number of IFN-γ producing γδ T cells is diminished. When a tumour develops, the IL-17-producing γδ T cells become activated in the lymph node, migrate to the tumour and create a pro-tumour microenvironment that’s associated with enhanced tumour growth.

To our surprise we found that organismal ageing does not impact on γδ T cell function on a cellular level.

Dr Maike de la Roche, Cancer Research UK Cambridge Institute

These results show that the γδ T cells pool in the lymph node are essential for shaping the balance between pro-tumour and anti-tumour immune responses. The bias towards the pro-tumour IL-17-producing γδ T cells lineage during ageing may be a crucial contributor to the increased tumour incidence with age.

Hung-Chang Chen, first author, said: “The function of lymph node resident γδ T cells is not well studied and I’m very excited to have uncovered a novel role of these cells in specifying the local tumour microenvironment.”

Maike de la Roche added:  “To our surprise we found that organismal ageing does not impact on γδ T cell function on a cellular level. Instead we have identified the mechanism by which ageing leads to a dramatic expansion of pro-tumour γδ T cells in the lymph nodes via signals received from the aged tissue. The next step is now to find out whether our findings hold true in the elderly”

Read more:

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

Dangerous γδ T cells in aged mice

1- Cancer Research UK Cancer Statistics

 

This work was made possible with the support of the Histopathology Core Facility.