Two commonly used chemotherapy drugs help tumors grow in mice by modulating the immune response, reports a study published online this week in Nature Medicine. The findings show how the immune system may limit the efficacy of some cancer chemotherapies.
The effect of cancer treatment drugs on the body’s natural immune responses that target tumors is much debated; whereas some studies suggest that chemotherapy is immunosuppressive, others report that it can increase antitumor immune responses.
Francois Ghiringhelli and colleagues found that two chemotherapeutics used in the clinic-5-fluorouracil and gemcitabine-activate a protein complex, Nlrp3 inflammasome, in myeloid derived suppressor cells. This activation leads to the release of the immune cell interleukin (IL)-1b, which then skews T immune cells to produce protumorigenic IL-17 and results in enhanced growth of tumors in mice.
The drugs were more efficacious at inhibiting tumor growth in mice lacking Nlrp3 or IL-17, or treated with an IL-1 receptor antagonist. The findings suggest that targeting the inflammasome pathway in conjunction with chemotherapy may improve its tumor killing efficacy by preventing the induction of protumorigenic immune responses.