Chemotherapy and targeted anti-cancer drugs can induce tumor cell senescence. Although cell proliferation is shut down in senescent cells, there is enhanced expression of secreted factors that may promote or suppress tumor growth.
Anna Vilgelm, Ph.D., and colleagues explored how therapy-induced senescence impacts the therapeutic response of melanoma. Using mouse models, the researchers assessed gene expression and immune cell recruitment in melanoma tumors after treatment with cell cycle inhibitors, which are known to induce senescence.
Melanoma tumors that responded to the inhibitors secreted the chemokine protein CCL5, which recruited immune cells to the tumor. The therapeutic response was greatly enhanced in mice that also received a T-cell activating immunotherapy. The researchers demonstrated that cell cycle inhibitors also induce CCL5 expression in human melanoma tumors.
The findings, reported in the Journal of the National Cancer Institute, suggest that combining therapy-induced senescence with T-cell-activating immunotherapies may improve outcomes for melanoma patients.
This research was supported by the Department of Veterans Affairs (MERIT grant and senior research career scientist award to Ann Richmond, Ph.D.), by a Harry J. Lloyd Charitable Trust award, and by grants from the National Institutes of Health (CA116021, CA090625, CA068485).
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