Immunostimulatory Effects of Radiotherapy for Local and Systemic Control of Melanoma: A Review

Abstract

Recently, modern therapies involving immune checkpoint inhibitors, cytokines, and oncolytic virus have been developed. Because of the limited treatment effect of modern therapy alone, the immunostimulatory effect of radiotherapy attracted increasing attention. The combined use of radiotherapy and modern therapy has been examined clinically and non-clinically, and its effectiveness has been confirmed recently. Because melanomas have high immunogenicity, better therapeutic outcomes are desired when using immunotherapy. However, sufficient therapeutic effects have not yet been achieved. Thus far, radiotherapy has been used only for local control of tumors. Although extremely rare, radiotherapy has also been reported for systemic control, i.e., abscopal effect. This is thought to be due to an antitumor immune response. Therefore, we herein summarize past information on not only the mechanism of immune effects on radiotherapy but also biomarkers reported in case reports on abscopal effects. We also reviewed the animal model suitable for evaluating abscopal effects. These results pave the way for further basic research or clinical studies on new treatment methods for melanoma. Currently, palliative radiation is administered to patients with metastatic melanoma for local control. If it is feasible to provide both systemic and local control, the treatment benefit for the patients is very large.

Long-Term Maintained Response to Selective Internal Radiation Therapy in an Oligometastatic Uveal Melanoma Patient Treated with Concomitant Anti-PD-1 Therapy

“…There is increasing evidence of a synergy between radiotherapy (RT) and IT. Radiation therapies can provoke a local and systemic immunomodulation and an increasing of the tumor mutation burden; both these effects can cooperate with immune checkpoint inhibitors to allow tumor-reactive T cells to mount a specific response [ 24 ]. This is meaningful, especially for UM: in fact, this tumor carries a lower mutation burden compared with cutaneous melanomas, although they share many antigens.…”

Patterns of Recurrence and Survival Rate After Complete Resection of Pathological Stage N2 Small-Cell Lung Cancer

“…In our study, the 2-year survival rate and 5-year survival rate of p-N2 patients who received TRT after complete resection were approximately 54% and 34%, respectively, which were better than those who did not receive TRT (P = 0.004) with or without chemotherapy. In recent years, "the abscopal effect" in non-small cell lung cancer caused concern, referring to an underlying immune response dependent on the microenvironment playing a significant role in trigging systemic antitumor effects after receiving radiotherapy combined with immune checkpoint inhibitors (20)(21)(22). However, the abscopal effect of radiotherapy on SCLC is still in research.…”

Recent Progress in Nanomedicine for Melanoma Theranostics With Emphasis on Combination Therapy

“…In addition to relying on inducing DNA damage, interrupting the cell cycle, and causing tumor cell death through apoptosis and necrosis, are considered the main mechanisms of radiotherapy with conventionally fractionated radiation. The radiotherapy can also induce neoantigen formation, tumor antigen presentation, and cytokine release to enhance immune responses ( Baskar et al, 2012 ; Takahashi and Nagasawa, 2020 ). Although radiotherapy often fails to eradicate the tumor completely, it is indeed another adjuvant treatment for the majority melanoma patients who were not suitable for surgical recession, or the advanced nodal disease or primary tumor after definitive resection ( Takahashi and Nagasawa, 2020 ).…”

“…The radiotherapy can also induce neoantigen formation, tumor antigen presentation, and cytokine release to enhance immune responses ( Baskar et al, 2012 ; Takahashi and Nagasawa, 2020 ). Although radiotherapy often fails to eradicate the tumor completely, it is indeed another adjuvant treatment for the majority melanoma patients who were not suitable for surgical recession, or the advanced nodal disease or primary tumor after definitive resection ( Takahashi and Nagasawa, 2020 ). Adjuvant postoperative radiotherapy may improve local-regional control (LRC) in patients at high-risk of locoregional recurrence after surgery alone; however, overall and disease-free survival rates appear unaffected by this approach ( Henderson et al, 2015 ; Mendenhall et al, 2017 ).…”