Roles of signaling pathways in cancer cells and immune cells in generation of immunosuppressive tumor-associated microenvironments

Yutaka Kawakami, Tomonori Yaguchi, Hidetoshi Sumimoto, Chie Kudo-Saito, Nobuo Tsukamoto, Tomoko Iwata-Kajihara, Shoko Nakamura, Hiroshi Nishio, Ryosuke Satomi, Asuka Kobayashi, Mayuri Tanaka, Jeong Hoon Park, Hajime Kamijuku, Takahiro Tsujikawa, Naoshi Kawamura

Research output: Chapter in Book/Report/Conference proceedingChapter

4 Citations (Scopus)


Cancer cells trigger multiple immunosuppressive cascades and generate immunosuppressive tumor-associated microenvironments including tumor and sentinel lymph nodes. Constitutive activation of various signaling pathways (e.g., MAPK, STAT3, NF-κB, β-catenin) in human cancer cells was found to trigger the multiple immunosuppressive cascades through the production of immunosuppressive cytokines, such as TGF-β, IL-10, IL-6, and VEGF, and induction of immunosuppressive immune cells, such as regulatory T cells, tolerogenic dendritic cells, and myeloid derived suppressor cells. Some of these cancer-derived cytokines impair various immune cells through activation of their signaling molecules such as STAT3 and NF-κB. Inhibitors for these activated signals could inhibit the multiple immunosuppressive cascades by acting on both cancer cells and immune cells. Since common signaling mechanisms are often utilized for some of the hallmarks of cancer (e.g., cell proliferation/survival, invasion/metastasis, and immunosuppression), targeting these common signaling pathways may be an attractive strategy for cancer therapy, including immunotherapy.

Original languageEnglish
Title of host publicationThe Tumor Immunoenvironment
PublisherSpringer Netherlands
Number of pages17
ISBN (Electronic)9789400762176
ISBN (Print)940076216X, 9789400762169
Publication statusPublished - 2013 Jan 1


  • BRAF
  • IL-10
  • Immunosuppression
  • MAPK
  • MDSC
  • NF-κB
  • Regulatory T cells
  • STAT3
  • TGF-β
  • β-catenin

ASJC Scopus subject areas

  • Medicine(all)


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