Immune cells build and maintain tumour defences

In tumours, clusters of immune cells can form that resemble lymph nodes: so-called tertiary lymphoid structures (TLS). They are seen as a sign of an active immune response. Patients whose tumours contain such structures tend to have a better prognosis across several cancer types. But how TLS form and are maintained was not yet clear.

The study, published in Science, shows that dendritic cells play a central role in establishing and maintaining these structures. Dendritic cells are specialised immune cells that activate and instruct other immune cells. Without their presence, tertiary lymphoid structures break down or fail to form.

What this means for immunotherapy

Immunotherapies, such as checkpoint inhibitors, work better in patients with an active immune response within the tumour. If dendritic cells are the key to forming those immune outposts, then stimulating these cells is a potential therapeutic target. The researchers suggest that therapies aimed at dendritic cells could strengthen or newly establish TLS, potentially increasing the effectiveness of existing immunotherapies.

This remains research in animal models and tissue samples. Translation to clinical treatments requires further validation. But the finding does provide a mechanistic explanation for why some tumours respond better to immunotherapy than others.

The link with ageing

Ageing impairs dendritic cell function. Older people have fewer functional dendritic cells and a generally less responsive immune system. That may help explain why older patients often have weaker anti-tumour immunity and respond less well to immunotherapy. From a longevity perspective, restoring dendritic cell function in older individuals is therefore an interesting direction for research.

Read the original article