Radiotherapy combined with immune checkpoint blockade immunotherapy: Achievements and challenges

Cancer Lett. 2015 Aug 28;365(1):23-9. doi: 10.1016/j.canlet.2015.05.012. Epub 2015 May 14.


To date, several kinds of immunomodulating monoclonal antibodies (mAbs) have been applied in clinical trials, such as anti-cytotoxic T-lymphocyte antigen-4 (anti-CTLA-4) mAb and anti-programmed death-1 (anti-PD-1) mAb. With the recent success of cancer immunotherapy, especially the checkpoint inhibitors, the renewed interest in immunotherapy as a treatment modality has gained extensive attention. The irradiated tumor cell death can enhance antitumor immunity by inducing antigen expression on tumor cells and activating lymphocytes. Radiotherapy (RT) combined with immunotherapy has revealed promising outcomes in various animal models. However, this new paradigm is often considered as a medical spectacle without a unifying model, and its mechanisms have yet to be elucidated. The purpose of this review is to investigate previously published studies of radiotherapy combined with checkpoint blockades by the following aspects: exploring the potential mechanisms; identifying the most beneficial dose, fraction and target site for RT; finding an appropriate time window to combine these two treatments; and discussing the toxicity and suitable treatment evaluating criteria.

Keywords: CTLA-4; Cancer treatment; Checkpoint; Immunotherapy; PD-L1; Radiotherapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Cell Cycle Checkpoints / drug effects*
  • Cell Proliferation / drug effects*
  • Chemoradiotherapy / adverse effects
  • Chemoradiotherapy / methods*
  • Dose Fractionation, Radiation
  • Humans
  • Immunotherapy / adverse effects
  • Immunotherapy / methods*
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Treatment Outcome


  • Antibodies, Monoclonal
  • Antineoplastic Agents