Senescent cells as vaccines against cancer

Cancer cells have a series of features that allow the immune system to identify and attack them. However, these same cells create an environment that blocks immune cells and protects the tumour. This means that immune cells cannot reach the cancer cells to remove them. The scientific community has been working for years to increase the effectiveness of the immune system against cancer by using vaccines based on dead tumour cells.

Scientists at IRB Barcelona, led by ICREA researcher Dr. Manuel Serrano, and Dr. Federico Pietrocola, now at the Karolinska Institutet, in Sweden, have studied how inducing senescence in cancer cells improves the effectiveness of the immune response to a greater degree than the dead cancer cells. After vaccinating healthy mice with senescent cancer cells and then stimulating the formation of tumours, the researchers observed that the animals did not develop cancer or that the number that do is significantly reduced. They also analysed the efficacy of vaccination in animals that had already developed tumours. In this setting, although the results were more moderate due to the protective barrier of the tumour, improvements were also observed.

“Our results indicate that senescent cells are a preferred option when it comes to stimulating the immune system against cancer, and they pave the way to considering vaccination with these cells as a possible therapy,” explains Dr. Serrano, head of the Cellular Plasticity and Disease lab at IRB Barcelona.

The researchers tested the technique in animal models of melanoma, a type of cancer characterised by high activation of the immune system, and also in pancreatic cancer models, which present strong barriers against immune cells. Prophylactic vaccination therapy with senescent cancer cells was effective against both types of tumors. They also complemented the study with tumour samples from cancer patients and confirmed that human cancer cells also have a greater capacity to activate the immune system when they are previously rendered senescent.

The group is now studying the combined efficacy of vaccination with senescent cells and immunotherapy treatments.

Senescence and its capacity to activate the immune system

Senescence is a state of latency reached by damaged or aged cells in which they do not reproduce but do not disappear either. Senescent cells emit information signals into their environment, which warn of their presence, stimulating an inflammatory response and tissue regeneration.

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