Radiotherapy combined with immunotherapy: the dawn of cancer treatment

Abstract

Radiotherapy (RT) is delivered for purposes of local control, but can also exert systemic effect on remote and non-irradiated tumor deposits, which is called abscopal effect. The view of RT as a simple local treatment has dramatically changed in recent years, and it is now widely accepted that RT can provoke a systemic immune response which gives a strong rationale for the combination of RT and immunotherapy (iRT). Nevertheless, several points remain to be addressed such as the interaction of RT and immune system, the identification of the best schedules for combination with immunotherapy (IO), the expansion of abscopal effect and the mechanism to amplify iRT. To answer these crucial questions, we roundly summarize underlying rationale showing the whole immune landscape in RT and clinical trials to attempt to identify the best schedules of iRT. In consideration of the rarity of abscopal effect, we propose that the occurrence of abscopal effect induced by radiation can be promoted to 100% in view of molecular and genetic level. Furthermore, the “radscopal effect” which refers to using low-dose radiation to reprogram the tumor microenvironment may amplify the occurrence of abscopal effect and overcome the resistance of iRT. Taken together, RT could be regarded as a trigger of systemic antitumor immune response, and with the help of IO can be used as a radical and systemic treatment and be added into current standard regimen of patients with metastatic cancer.

Radiation-induced PD-L1 expression in tumor and its microenvironment facilitates cancer-immune escape: a narrative review

“…The cell death that can activate downstream immune responses and stimulate immune surveillance is characterized as immunogenic and this leads to the "in situ" vaccination effect (12,13). Increasing evidence indicates the immunomodulatory effects of RT in systemic antitumor responses (14)(15)(16). Strikingly, a phenomenon observed in clinical case reports, termed the radiation-dependent abscopal effect, signifies tumor regression outside the irradiated fields (17,18).…”

Local Graft Irradiation for Acute, Medication Refractory Transplant Rejection of a Pancreas Alone Graft: A Case Report

“… 19 However, additional possible mechanisms may be extrapolated from the effects of radiation on the microenvironment in cancer literature. 20 Following low-dose total body radiation, CD4+ CD25+ Foxp3 + T regulatory (Treg) cells show increased survival compared with other lymphocytes, suggesting radiation resistance of Tregs. 19 , 21 Additionally, low-dose radiation has been shown to recruit Tregs to the local microenvironment.…”

Immune checkpoint blockade for locally advanced or recurrent/metastatic cervical cancer: An update on clinical data

“…While anti-angiogenic therapy and radiotherapy regulate the immunosuppressive microenvironment, immunotherapy increases the sensitivity of radiotherapy. Indeed, the combination of an activated immune response and multiple therapies can have a synergistic anti-tumor effect ( 54 – 56 ). On October 13, 2021, Pembrolizumab in combination with chemotherapy, with or without Bevacizumab, was approved by the U.S. FDA for first-line treatment of R/M CC with CPS ≥1.…”