What is the relationship between cancer and senescent cells?

Senescent cells, also known as aged cells, are cells that have permanently stopped dividing. That may sound harmless, but their relationship with cancer is twofold and nuanced. On one hand, senescence acts as a built-in safety mechanism: cells that are at risk of becoming malignant are forced into that permanent standstill. Escaping that mechanism is a well-known step toward cancer.

The other side of the picture emerges when senescent cells accumulate in tissue, as happens with ageing. They then secrete a mixture of inflammatory substances known as the SASP. That inflammatory environment can actually fuel tumour growth rather than suppress it. Ageing also weakens the immune system, making it less effective at detecting and clearing cancer cells. This connection is plausible but has not yet been fully explained.

In specific cancer types, senescence of immune cells plays a concrete role. In lung cancer, aged lung macrophages (immune cells) accumulated early in the tumour in mouse models. They suppressed the immune response and promoted tumour growth; removing those cells reduced tumour development. Comparable cells have also been found in human lung cancer tissue. In prostate cancer, tumour cells drive neutrophils (a type of white blood cell) into a senescent state via a protein-signalling pair, after which those cells suppress the immune defence; high levels of those proteins were associated with a worse prognosis.

Cancer treatment itself is also part of the story. Chemo- and radiotherapy can push tumour cells into a senescent state, which is initially helpful. But the inflammatory substances secreted by those senescent tumour cells can activate dormant cancer stem cells, thereby increasing the risk of recurrence. That is a genuine concern, although this evidence comes largely from laboratory studies. In triple-negative breast cancer, researchers observed that the patient's own immune cells could become senescent, causing modern immunotherapy to work less effectively.

Science is searching for ways to purposefully exploit or reverse the senescence of cells. An experimental approach in which specialised immune cells (CAR-T cells) are used to selectively clear senescent cells extended survival in mice with lung cancer, but this has so far been seen only in animal research. More accurately identifying senescent cells in tissue remains an active area of research, because anyone who can better detect those cells can intervene in a more targeted way.