Cellular senescence is a stress response that activates innate immune cells, yet little is known about its interplay with the adaptive immune system. Senescent cells are unique in that they eventually stop multiplying but don’t die off when they should. However, not all senescent cells are bad. The molecules and compounds expressed by senescent cells play important roles across the lifespan, including in embryonic development, childbirth, and wound healing. Now scientists at IRB Barcelona, led by ICREA researcher Manuel Serrano, PhD, and Federico Pietrocola, PhD, now at the Karolinska Institute have studied how inducing senescence in cancer cells improves the effectiveness of the immune response to a greater degree than dead cancer cells.
Their findings demonstrate that after vaccinating healthy mice with senescent cancer cells and then stimulating the formation of tumors, the animals did not develop cancer or have a reduced number of tumors.
The findings, “Cellular senescence is immunogenic and promotes anti-tumor immunity,” are published in the journal Cancer Discovery.
“Here, we show that senescent cells combine several features that render them highly efficient in activating dendritic cells (DCs) and antigen-specific CD8 T cells,” wrote the researchers. “This includes the release of alarmins, activation of interferon signaling, enhanced MHC class I machinery, and presentation of senescence-specific self-peptides that can activate CD8 T cells.”
“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,” explained Serrano, who is 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 characterized by high activation of the immune system, and also in pancreatic cancer models, which present strong barriers against immune cells.
The researchers are now studying the combined efficacy of vaccination with senescent cells and immunotherapy treatments.
“Our study concludes that the induction of senescence in tumor cells improves the recognition of these cells by the immune system and it also increases the intensity of the response they generate. So our findings are very positive,” explained Inés Marín, a doctoral student from the same laboratory and first author of the study.
The researchers believe other diseases related to aging and those in which there is a prevalent presence of senescent cells may also benefit from possible vaccines with senescent cells.