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.

Clinical Trials of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma

“…A different approach to improve the response is to modulate the immunogenicity of tumors or to boost the immune system by combination of locoregional and/or radiotherapy with immunotherapy. Thus, local therapy, such as radiofrequency ablation, TACE, SIRT or radiotherapy, may promote an immune response via the influence of the TME [ 89 , 90 , 91 ]. This approach is based on releasing tumor antigens through cell death induced by locoregional therapy, which subsequently improves immunotherapy due to better antigen presentation.…”

The Repression of Matrix Metalloproteinases and Cytokine Secretion in Glioblastoma by Targeting K+ Channel

“…Immune system dysregulation is considered as one of the pivotal mechanism in pathophysiology of numerous tumors (Voutsadakis, 2018a(Voutsadakis, , 2018b. Moreover, selective and non-selective ion channels are also considered important in physiopathology of several cancers including GBM (Morelli et al, 2016).…”

A Systematic Review and Meta-analysis of PD-1 and PD-L1 Inhibitors Monotherapy in Metastatic Gastric and Gastroesophageal Junction Adenocarcinoma

“…Immune blockade inhibitors have been studied in clinical trials for many common gastrointestinal cancers. 16 Gastric and gastroesophageal junction adenocarcinomas constitute one of the gastrointestinal cancer groups where ICIs have been investigated. Results of these trials have been encouraging in subsets of patients and regulatory approval has been granted by the USFDA to the PD-L1 inhibitor pembrolizumab for gastric gastroesophageal junction adenocarcinomas that express PD-L1.…”