Tumor cure by radiation therapy and checkpoint inhibitors depends on pre-existing immunity

Sci Rep. 2018 May 3;8(1):7012. doi: 10.1038/s41598-018-25482-w.

Abstract

Radiation therapy is a source of tumor antigen release that has the potential to serve as an endogenous tumor vaccination event. In preclinical models radiation therapy synergizes with checkpoint inhibitors to cure tumors via CD8 T cell responses. To evaluate the immune response initiated by radiation therapy, we used a range of approaches to block the pre-existing immune response artifact initiated by tumor implantation. We demonstrate that blocking immune responses at tumor implantation blocks development of a tumor-resident antigen specific T cell population and prevents tumor cure by radiation therapy combined with checkpoint immunotherapy. These data demonstrate that this treatment combination relies on a pre-existing immune response to cure tumors, and may not be a solution for patients without pre-existing immunity.

Publication types

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

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / radiotherapy*
  • Animals
  • Antineoplastic Agents / administration & dosage
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / radiotherapy
  • Combined Modality Therapy / methods*
  • Disease Models, Animal
  • Immunologic Factors / administration & dosage*
  • Immunotherapy / methods*
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Neoplasm Transplantation
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / radiotherapy
  • Radiotherapy / methods*
  • Transplantation, Heterologous
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Immunologic Factors