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Review
. 2024 Oct 2;46(10):11075-11085.
doi: 10.3390/cimb46100658.

A Comprehensive Revision of Radiation Immunotherapy and the Abscopal Effect in Central Nervous System Metastases: Reassessing the Frontier

Júlia Moscardini-Martelli  1 , Alejandro Rodríguez-Camacho  1   2 , Jorge Alejandro Torres-Ríos  1 , Juan Marcos Meraz-Soto  1 , José Guillermo Flores-Vázquez  1 , Laura Crystell Hernández-Sánchez  1 , Francisco Javier Lozano-Ruiz  2 , Federico Maldonado-Magos  2 , Dharely Cid-Sánchez  2 , Christian Haydeé Flores-Balcázar  2 , Miguel Ángel Celis-López  1 , Guillermo Axayacatl Gutiérrez-Aceves  1 , Fabiola Flores-Vázquez  3 , Sergio Moreno-Jiménez  1   4
Affiliations
Review

A Comprehensive Revision of Radiation Immunotherapy and the Abscopal Effect in Central Nervous System Metastases: Reassessing the Frontier

Júlia Moscardini-Martelli et al. Curr Issues Mol Biol. .

Abstract

Seventy years ago, Robin Mole introduced the concept of the abscopal effect to describe a rare phenomenon. This occurs when local radiation triggers an immune-mediated reduction in tumors outside the treated area but within the same organism. Observing this effect has been linked to improved overall and progression-free survival in patients who experience it. While the abscopal effect was once considered rare, it is now being observed more frequently due to the combination of radiation with immunotherapy. As a result, more researchers are exploring this study area, which shows promise for excellent results. This review focuses explicitly on the immunological implications of activating the abscopal effect through ionizing radiation in the central nervous system and explores the potentially involved immunological pathways.

Keywords: abscopal effect; immunotherapy; metastasis; oncology; radiosurgery; radiotherapy.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Immunologic basis of abscopal mechanisms. Following irradiation of the brain tumor, the DNA is broken into double-stranded structures, leading to IFN production. IFN triggers the sting pathway in dendritic cells and promotes anti-tumor CD8+ T cells in the lymph nodes. Furthermore, once exposed to radiation, tumor cells release antigens that are taken up by dendritic cells, which migrate to the lymph nodes and trigger naive T cells, which convert into cytotoxic T cells with the ability to migrate from the lymph nodes to distant tumor sites. Radiation-induced immunogenic cell death leads to the production of heat shock proteins (HSP), high-motility group box 1 (HMGB1), glucose-regulated protein 96 (GP96), and damage-associated molecular patterns (DAMPS), which increase dendritic cell activation through the toll-like receptor 4 (TLR4) pathway. Surviving irradiated cells increase the expression of death receptors, such as Fas, allowing an increased recognition by antitumor CD8+ T cells. Cancer cells express PD-L1 ligands, activated T cells contain programmed death receptor 1 (PD-1), and the PD-1 receptor interacts with PD-L1, enabling tumor cells to avoid recognition by the immune system. It is possible to enhance the reaction of the abscopal response by combining radiation and monoclonal antibodies of checkpoint inhibitor therapy. Created with BioRender.com.
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