Immune blockade inhibitors and the radiation abscopal effect in gastrointestinal cancers

Abstract

The field of tumor immunology has produced in the recent years a revolution in cancer therapeutics putting an end in the long lasting frustration of investigators in the area stemming from largely unsuccessful strides to develop cancer vaccines. This progress has come from the introduction of immune checkpoint inhibitors, monoclonal antibodies blocking ligand/receptor pairs with inhibitory effects for immune cells. Through this blockade immune checkpoint blockers are able to activate the immune system and create an anti-tumoral effect. A significant sub-set of patients with various types of cancers such as melanoma, lung carcinomas and urothelial cancers benefit from treatment with these drugs and survivals have improved in some cases. However other cancers are primarily resistant to immune blockers and secondary resistance is also the norm. Radiation therapy is often used in the palliative treatment of patients with advanced cancers and, in addition to the local effect in the irradiated field, it may in rare cases produce a systemic antitumor effect, termed “abscopal”. This effect has been suggested to be produced by immune mechanisms. Thus an opportunity presents for a synergistic effect of immune stimulation between radiation and immune blockade inhibitors. The therapeutic opportunities presented with the combination of radiation and these drugs for gastrointestinal cancers will be discussed in this editorial overview.

Keywords: Abscopal effect, Radiation, CD28/cytotoxic T-lymphocyte antigen-4, Immune blockade inhibitors, Programmed death 1, Programmed death ligand-1

Core tip: Immune checkpoint inhibitors activate the immune response to tumors by blocking inhibitory receptor pairs. Radiation treatment may also promote anti-tumor immune response. Thus, there exist an opportunity for synergy between the two treatment modalities that may be exploited therapeutically in gastrointestinal and other cancers.