Cellular senescence and immune response in breast cancer

Cellular senescence is a state acquired by damaged cells, which protects the body from cancer, and is characterized by irreversible cell cycle arrest. The senescent cells’ morphology and metabolism change and they adopt a Senescence Associated Secretory Phenotype. The SASP involves the secretion of cytokines, growth factors and extracellular-matrix-modifying enzymes that can exert paracrine signals on their environment. In various cancers, cellular senescence has been observed, but it is unclear which cells become senescent, and how they influence disease progression. While for the senescent cells themselves this mechanism is a tumor-suppressor one, blocking proliferation, they can elicit non-cell-autonomous effects: the secreted factors may create an immune-protected environment, and promote tumorigenesis.

I aim to uncover the function of senescent cells within breast cancer(BC). Specifically, I am studying the means by which senescent cells in BC influence immune system reaction, with a focus on the interferon response

We have observed a strong activation of the immune response genes in therapy induced senescence in cultured BC and supportive cells, as well as in transgenic mouse models, in which we can induce senescence in BCs or their environment through activation of the p16 gene.

I found that senescent cancer cells respond to interferon with an upregulation of antigen presentation genes and other immune response genes, suggesting that these cells have an elevated immune activating response.

These analyses will allow a better understanding of the influence of senescence on the immune system in BC and open novel approaches of treatment exploiting the senescent cells vulnerabilities.