Strategies for combining immunotherapy with radiation for anticancer therapy

Immunotherapy. 2015;7(9):967-980. doi: 10.2217/imt.15.65. Epub 2015 Aug 27.

Abstract

Radiation therapy controls local disease but also prompts the release of tumor-associated antigens and stress-related danger signals that primes T cells to promote tumor regression at unirradiated sites known as the abscopal effect. This may be enhanced by blocking inhibitory immune signals that modulate immune activity through a variety of mechanisms. Indeed, abscopal responses have occurred in patients with lung cancer or melanoma when given anti-CTLA4 antibody and radiation. Other approaches involve expanding and reinfusing T or NK cells or engineered T cells to express receptors that target specific tumor peptides. These approaches may be useful for immunocompromised patients receiving radiation. Preclinical and clinical studies are testing both immune checkpoint-based strategies and adoptive immunotherapies with radiation.

Keywords: CAR T cells; OX40; abscopal effect; immune checkpoints; immunotherapy; ipilimumab; lung cancer; melanoma; nivolumab; radiation.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use*
  • Antigens, Neoplasm / immunology
  • CTLA-4 Antigen / immunology
  • Genetic Engineering
  • Humans
  • Immunocompromised Host
  • Immunotherapy, Adoptive*
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / transplantation*
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / radiation effects
  • Neoplasm Metastasis
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Radioimmunotherapy*
  • Receptors, Antigen, T-Cell / genetics
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / radiation effects
  • T-Lymphocytes / transplantation*

Substances

  • Antibodies, Monoclonal
  • Antigens, Neoplasm
  • CTLA-4 Antigen
  • Receptors, Antigen, T-Cell