Research press release


Nature Medicine

Chemotherapy blunts immunity against tumor


Francois Ghiringhelliたちは、臨床で使用されている2種類の化学療法薬(5-フルオロウラシルとゲムシタピン)が、骨髄由来サプレッサー細胞でNlrp3インフラマソームというタンパク質複合体を活性化することを発見した。この活性化がインターロイキン(IL)-1βの放出を引き起こし、つぎにこのIL-1βが、T細胞に腫瘍形成促進性のIL-17を生産させる。その結果、マウスの腫瘍の成長が促進される。


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.

doi: 10.1038/nm.2999


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