Chemotherapy-Induced IL34 Enhances Immunosuppression by Tumor-Associated Macrophages and Mediates Survival of Chemoresistant Lung Cancer Cells

• Baghdadi, Muhammad

• Wada, Haruka

• Nakanishi, Sayaka

• Abe, Hirotake

• Han, Nanumi

• Putra, Wira Eka

• Endo, Daisuke

• Watari, Hidemichi

• Sakuragi, Noriaki

• Hida, Yasuhiro

• Kaga, Kichizo

• Miyagi, Yohei

• Yokose, Tomoyuki

• Takano, Atsushi

• Daigo, Yataro

• Seino, Ken-ichiro

Bibliographic Information

Other Title

• An importance of IL-34 in cancer chemoresistance

Abstract

The 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.

Journal

• Cancer research

  Cancer research 76 (20), 6030-6042, 2016-10

  American Association for Cancer Research

Keywords

• Cancer Research
• Oncology

Details

• CRID: 1050282677651820800
• NII Article ID: 120006347198
• DOI: 10.1158/0008-5472.can-16-1170
• ISSN: 15387445
• ISSN: 00085472
• HANDLE: 2115/67225
• Web Site: https://aacrjournals.org/cancerres/article-pdf/76/20/6030/2740431/6030.pdf
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN