Emerging Role of the Unfolded Protein Response in Tumor Immunosurveillance

Trends Cancer. 2017 Jul;3(7):491-505. doi: 10.1016/j.trecan.2017.05.005. Epub 2017 Jul 6.

Abstract

Disruption of endoplasmic reticulum (ER) homeostasis results in ER stress and activation of the unfolded protein response (UPR). This response alleviates cell stress, and is activated in both tumor cells and tumor infiltrating immune cells. The UPR plays a dual function in cancer biology, acting as a barrier to tumorigenesis at the premalignant stage, while fostering cancer maintenance in established tumors. In infiltrating immune cells, the UPR has been involved in both immunosurveillance and immunosuppressive functions. This review aims to decipher the role of the UPR at different stages of tumorigenesis and how the UPR shapes the balance between immunosurveillance and immune escape. This knowledge may improve existing UPR-targeted therapies and the design of novel strategies for cancer treatment.

Keywords: cancer; immune cells; immune escape; immunosurveillance; unfolded protein response.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Apoptosis
  • Carcinogenesis / immunology
  • Cell Transformation, Neoplastic / immunology
  • Endoplasmic Reticulum / metabolism
  • Endoplasmic Reticulum Stress / immunology*
  • Humans
  • Immunity, Cellular / immunology
  • Monitoring, Immunologic*
  • Neoplasm Staging
  • Neoplasms / diagnosis*
  • Neoplasms / drug therapy
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Signal Transduction / immunology*
  • Tumor Escape / immunology
  • Unfolded Protein Response / drug effects
  • Unfolded Protein Response / immunology*

Substances

  • Antineoplastic Agents