Improvement of cancer immunotherapy by combining molecular targeted therapy

Yutaka Kawakami, Tomonori Yaguchi, Hidetoshi Sumimoto, Chie Kudo-Saito, Tomoko Iwata-Kajihara, Shoko Nakamura, Takahiro Tsujikawa, Jeong Hoon Park, Boryana K. Popivanova, Junichiro Miyazaki, Naoshi Kawamura

Research output: Contribution to journalShort surveypeer-review

17 Citations (Scopus)

Abstract

In human cancer cells, a constitutive activation of MAPK, STAT3, β-catenin, and various other signaling pathways triggers multiple immunosuppressive cascades. These cascades result in the production of immunosuppressive molecules (e.g., TGF-β, IL-10, IL-6, VEGF, and CCL2) and induction of immunosuppressive immune cells (e.g., regulatory T cells, tolerogenic dendritic cells, and myeloid-derived suppressor cells). Consequently, immunosuppressive conditions are formed in tumor-associated microenvironments, including the tumor and sentinel lymph nodes. Some of these cancer-derived cytokines and chemokines impair immune cells and render them immunosuppressive via the activation of signaling molecules, such as STAT3, in the immune cells. Thus, administration of signal inhibitors may inhibit the multiple immunosuppressive cascades by acting simultaneously on both cancer and immune cells at the key regulatory points in the cancer-immune network. Since common signaling pathways are involved in manifestation of several hallmarks of cancer, including cancer cell proliferation/survival, invasion/metastasis, and immunosuppression, targeting these shared signaling pathways in combination with immunotherapy may be a promising strategy for cancer treatment.

Original languageEnglish
Article numberArticle 136
JournalFrontiers in Oncology
Volume3 MAY
DOIs
Publication statusPublished - 2013

Keywords

  • Immunosuppression
  • Immunotherapy
  • MAPK
  • STAT3
  • β-catenin

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Improvement of cancer immunotherapy by combining molecular targeted therapy'. Together they form a unique fingerprint.

Cite this