Immune recognition of irradiated cancer cells Review uri icon

Overview

MeSH Major

  • Antineoplastic Agents
  • Immunotherapy
  • Molecular Targeted Therapy
  • Neoplasms

abstract

  • Ionizing irradiation has been extensively employed for the clinical management of solid tumors, with therapeutic or palliative intents, for decades. Until recently, radiation therapy (RT) was believed to mediate antineoplastic activity mostly (if not only) as a consequence of cancer cell-intrinsic effects. Indeed, the macromolecular damage imposed to malignant cells by RT initiates one or multiple signal transduction cascades that drive a permanent proliferative arrest (cellular senescence) or regulated cell death. Both these phenomena show a rather linear dose-response correlation. However, RT also mediates consistent immunological activity, not only as an "on-target effect" originating within irradiated cancer cells, but also as an "off-target effect" depending on the interaction between RT and stromal, endothelial, and immune components of the tumor microenvironment. Interestingly, the immunological activity of RT does not exhibit linear dose-response correlation. Here, we discuss the mechanisms whereby RT alters the capacity of the immune system to recognize and eliminate irradiated cancer cells, either as an "on-target" or as on "off-target" effect. In particular, we discuss the antagonism between the immunostimulatory and immunosuppressive effects of RT as we delineate combinatorial strategies to boost the former at the expenses of the latter.

publication date

  • November 2017

Research

keywords

  • Review

Identity

Language

  • eng

PubMed Central ID

  • PMC5659195

Digital Object Identifier (DOI)

  • 10.1111/imr.12568

PubMed ID

  • 29027232

Additional Document Info

start page

  • 220

end page

  • 230

volume

  • 280

number

  • 1