Targeting tumors with LIGHT to generate metastasis-clearing immunity

Cytokine Growth Factor Rev. 2008 Jun-Aug;19(3-4):285-94. doi: 10.1016/j.cytogfr.2008.04.004. Epub 2008 May 27.

Abstract

Metastatic diseases cause the majority of morbidity and mortality of cancer patients. Established tumors form both physical and immunological barriers to limit immune detection and destruction. Current immunotherapy of vaccination and adoptive transfer shows limited effect at least in part due to the existing barriers in the tumors and depending on the knowledge of tumor antigens. Tumor necrosis factor (TNF) superfamily (TNFSF) member 14 (TNFSF14) LIGHT interacts with stromal cells, dendritic cells (DCs), NK cells, naïve and activated T cells and tumor cells inside the tumor tissues via its two functional receptors, HVEM and lymphotoxin beta receptor (LTbetaR). Targeting tumor tissues with LIGHT leads to augmentation of priming, recruitment, and retention of effector cells at tumor sites, directly or indirectly, to induce strong anti-tumor immunity to inhibit the growth of primary tumors as well as eradicate metastases. Intratumor treatment would break tumor barriers and allow strong immunity against various tumors without defining tumor antigens. This review summarizes recent findings to support that LIGHT is a promising candidate for an effective cancer immunotherapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Genetic Therapy
  • Humans
  • Immunotherapy
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Mice
  • Neoplasm Metastasis / immunology
  • Neoplasm Metastasis / therapy*
  • Neoplasms / immunology*
  • T-Lymphocytes / immunology
  • T-Lymphocytes, Cytotoxic / immunology
  • Tumor Necrosis Factor Ligand Superfamily Member 14 / genetics
  • Tumor Necrosis Factor Ligand Superfamily Member 14 / metabolism*

Substances

  • Tumor Necrosis Factor Ligand Superfamily Member 14