Treatment of Cancer with Radio-Immunotherapy: What We Currently Know and What the Future May Hold

Abstract

Radiotherapy and immunotherapy are most effective as cancer therapies in the setting of low-volume disease. Although initial studies of radio-immunotherapy in patients with metastatic cancer have not confirmed the efficacy of this approach, the role of radio-immunotherapy in patients with limited metastatic burden is unclear. We propose that further investigation of radio-immunotherapy in metastatic patients should focus upon patients with oligometastatic disease.

Immunotherapy and Radiotherapy as an Antitumoral Long-Range Weapon—A Partnership with Unsolved Challenges: Dose, Fractionation, Volumes, Therapeutic Sequence

“…The regimen that associates pembrolizumab with radiotherapy (30Gy in five fractions) is feasible and well tolerated, but the study did not reach its survival objectives. MYB/NFIB translocation and PD-L1 expression were associated with the local response rate to the combined treatment [ 18 , 19 ].…”

“…Vascular permeability has been used as a surrogate marker for tumor immune activation in preclinical models. An increase in this biomarker was recorded after the first 24 hours after irradiation, and after 3-10 days a reduction to the baseline level was observed [ 19 ]. A study that combined immunotherapy with CTLA-4 inhibitors in malignant melanoma with brain metastases showed better results in OS if single-fraction stereotactic radiosurgery (SRS) was performed before ipilimumab administration or concomitantly, relative to the situation in which immunotherapy was initiated before irradiation.…”

Combined radio-immunotherapy: An opportunity to increase the therapeutic ratio of oligometastasis-directed radiotherapy

“…As previously reviewed, currently reported trials of radio-immunotherapy in the treatment of patients with metastatic disease vary in a number of important ways, which along with the potentially immunosuppressive effects of radiotherapy may contribute to the negative results of the majority of these studies [ 30 , 31 ]. However, given that the aforementioned prospective studies include patients with extensive metastatic burden with at least one metastasis not treated with local therapy, it is likely that, as is the case when radiotherapy and immunotherapy are used as monotherapies, combined radio-immunotherapy is most effective as a treatment for metastatic cancer in patients with low-volume disease, thus explaining the negative results of currently reported studies.…”

Identification of RP11‐770J1.4 as immune‐related lncRNA regulating the CTXN1–cGAS–STING axis in histologically lower‐grade glioma

“…Immunotherapy, which involves modulating the function of the immune system through stimulatory or inhibitory mechanisms mediated by immune checkpoint molecules, has been used with great success in solid tumors 31 . However, clinical trials targeting immune checkpoints have not shown improved survival benefits in GBM patients 32–34 . Blockade of negative feedback signals from immune checkpoints can provoke an immune response in the body, which in turn promotes T cell activity to kill tumors.…”