Cancer-induced immunosuppressive cascades and their reversal by molecular-targeted therapy

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: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Immunological status in tumor tissues varies among patients. Infiltration of memory-type CD8+ T cells into tumors correlates with prognosis of patients with various cancers. However, the mechanism of the differential CD8+ T cell infiltration has not been well investigated. In general, tumor-associated microenvironments, including tumor and sentinel lymph nodes, are under immunosuppressive conditions such that the immune system is not able to eliminate cancer cells without immune-activating interventions. Constitutive activation of various signaling pathways in human cancer cells triggers multiple immunosuppressive cascades that involve various cytokines, chemokines, and immunosuppressive cells. Signaling pathway inhibitors could inhibit these immunosuppressive cascades by acting on either cancer or immune cells, or both. In addition, common signaling mechanisms are often utilized for multiple hallmarks of cancer (e.g., cell proliferation/survival, invasion/metastasis, and immunosuppression). Therefore, targeting these common signaling pathways may be an attractive strategy for cancer therapy including immunotherapy.

Original languageEnglish
Pages (from-to)80-86
Number of pages7
JournalAnnals of the New York Academy of Sciences
Volume1284
Issue number1
DOIs
Publication statusPublished - 2013 May

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Keywords

  • BRAF
  • Immunosuppression
  • NF-κB
  • STAT3
  • β-catenin

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

Cite this

Kawakami, Y., Yaguchi, T., Sumimoto, H., Kudo-Saito, C., Tsukamoto, N., Iwata-Kajihara, T., Nakamura, S., Nishio, H., Satomi, R., Kobayashi, A., Tanaka, M., Park, J. H., Kamijuku, H., Tsujikawa, T., & Kawamura, N. (2013). Cancer-induced immunosuppressive cascades and their reversal by molecular-targeted therapy. Annals of the New York Academy of Sciences, 1284(1), 80-86. https://doi.org/10.1111/nyas.12094