Emerging biomarkers for the combination of radiotherapy and immune checkpoint blockers

Semin Cancer Biol. 2018 Oct;52(Pt 2):125-134. doi: 10.1016/j.semcancer.2017.12.007. Epub 2017 Dec 16.

Abstract

Over the past few years, multiple immune checkpoint blockers (ICBs) have achieved unprecedented clinical success and have been approved by regulatory agencies for the treatment of an increasing number of malignancies. However, only a limited fraction of patients responds to ICBs employed as a standalone intervention, calling for the development of combinatorial regimens. Radiation therapy (RT) stands out as a very promising candidate for this purpose. Indeed, RT mediates antineoplastic effects not only by cytotoxic and cytostatic mechanisms, but also by modulating immunological functions, both locally (within the irradiated field) and systemically. As combinatorial regimens involving RT and ICBs are being developed and clinically tested at an accelerating pace, it is paramount to identify biomarkers that reliably predict the likelihood of individual patients to respond. Here, we discuss emerging biomarkers that may potentially predict the response of cancer patients to RT plus ICBs.

Keywords: DNA damage response; Mutational load; Natural killer cells; PD-L1; Type I interferon.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / immunology
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / immunology*
  • Humans
  • Neoplasms / immunology
  • Neoplasms / radiotherapy*
  • Neoplasms / therapy*
  • Radiotherapy / methods

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor