Could senescent tumor cells offer a new cancer vaccine strategy?
Scientists have found that senescent tumor cells induce a bigger immune response than dead cancer cells, which could lead to a senescent cell cancer vaccine.
Researchers affiliated with the Institute for Research in Biomedicine Barcelona (IRB Barcelona; Spain) led by Manuel Serrano and Federico Pietrocola have found that senescent tumor cells induce a bigger immune response than dead cancer cells. When researchers subsequently induced tumor formation in mice injected with the senescent tumor cells, they found the mice developed fewer tumors, with some developing none. Although the injection was less effective against existing tumors, this research suggests that a potential senescent cell cancer vaccine could show promise.
Senescence is a state where cells neither function normally nor die. Cells that are damaged or old may enter this suspended state in which they do not reproduce but still interact with their surroundings via cellular signaling. Researchers have previously suggested that this interaction causes an innate immune response characterized by inflammation but have not assessed senescent cells’ interactions with the adaptive immune system.
To test the size and potential utility of this immune response, the researchers induced senescence in melanoma and pancreatic tumor cells prior to injecting them into mice. They assessed the immune response to this senescent cell cancer vaccine and its potential to prevent and treat tumors by using mice with and without pre-existing tumors.
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When the scientists vaccinated mouse models prior to inducing tumor formation, they recorded that the mice injected with senescent cells developed fewer tumors with some developing none at all. Assessing the impact of vaccinating mice with existing tumors, the scientists observed more modest improvements, with researchers concluding that the tumors’ protective barrier reduced the impact of adaptive immune system activation.
Their results were supported by an additional study conducted as a collaboration between IRB Barcelona and Memorial Sloan Kettering Cancer Center (NY, USA). The two studies indicated that senescent cells potently activate the adaptive immune system, including dendritic cells and CD8 T-cells.
The researchers believe that senescent cells offer a potential cancer vaccination as they are more effectively identified by the immune system and, as living cells, remain in the body, stimulating the immune system for longer. First author of the study, Inés Marín, explained: “Our study concludes that the induction of senescence in tumour 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.”
The researchers plan to assess the impact of the senescent cell cancer vaccine in combination with immunotherapies.
