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

Ann N Y Acad Sci. 2013 May:1284:80-6. doi: 10.1111/nyas.12094.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / cytology
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Immunotherapy / methods*
  • MAP Kinase Signaling System
  • Mice
  • Molecular Targeted Therapy / methods*
  • NF-kappa B / metabolism
  • Neoplasms / immunology*
  • Neoplasms / therapy
  • Proto-Oncogene Proteins B-raf / metabolism
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction
  • beta Catenin / metabolism

Substances

  • Immunosuppressive Agents
  • NF-kappa B
  • STAT3 Transcription Factor
  • beta Catenin
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf