2024-03-29T07:26:57Zhttps://eprints.lib.hokudai.ac.jp/dspace-oai/requestoai:eprints.lib.hokudai.ac.jp:2115/672252022-11-17T02:08:08Zhdl_2115_20058hdl_2115_149Chemotherapy-Induced IL34 Enhances Immunosuppression by Tumor-Associated Macrophages and Mediates Survival of Chemoresistant Lung Cancer CellsAn importance of IL-34 in cancer chemoresistanceBaghdadi, MuhammadWada, HarukaNakanishi, SayakaAbe, HirotakeHan, NanumiPutra, Wira EkaEndo, DaisukeWatari, HidemichiSakuragi, NoriakiHida, YasuhiroKaga, KichizoMiyagi, YoheiYokose, TomoyukiTakano, AtsushiDaigo, YataroSeino, Ken-ichiro490The ability of tumor cells to escape immune destruction and their acquired resistance to chemotherapy are major obstacles to effective cancer therapy. Although immune checkpoint therapies such as anti-PD-1 address these issues in part, clinical responses remain limited to a subpopulation of patients. In this report, we identified IL34 produced by cancer cells as a driver of chemoresistance. In particular, we found that IL34 modulated the functions of tumor-associated macrophages to enhance local immunosuppression and to promote the survival of chemoresistant cancer cells by activating AKT signaling. Targeting IL34 in chemoresistant tumors resulted in a remarkable inhibition of tumor growth when accompanied with chemotherapy. Our results define a pathogenic role for IL34 in mediating immunosuppression and chemoresistance and identify it as a tractable target for anticancer therapy.American Association for Cancer ResearchJournal Articleapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/2115/67225https://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/67225/1/CancerRes76_6030.pdfhttps://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/67225/2/Captions_SupplFiles.pdfhttps://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/67225/3/Supplementary_figure_S1.pdfhttps://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/67225/4/Supplementary_figure_S2.pdfhttps://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/67225/5/Supplementary_figure_S3.pdfhttps://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/67225/6/Supplementary_figure_S4.pdfhttps://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/67225/7/Supplementary_figure_S5.pdfhttps://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/67225/8/Supplementary_figure_S6.pdfhttps://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/67225/10/Supplementary_materials_and_methods.pdfhttps://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/67225/9/Supplementary_tables.pdf0008-5472Cancer research7620603060422016-10enginfo:pmid/27550451info:doi/10.1158/0008-5472.CAN-16-1170author