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Review
. 2024 Apr 4:4:1331364.
doi: 10.3389/fnume.2024.1331364. eCollection 2024.

Immunological effects of radiopharmaceutical therapy

Amanda G Shea #  1 , Malick Bio Idrissou #  2 , Ana Isabel Torres  1 , Tessa Chen  1 , Reiner Hernandez  2   3 , Zachary S Morris  1   3 , Quaovi H Sodji  1   3
Affiliations
Review

Immunological effects of radiopharmaceutical therapy

Amanda G Shea et al. Front Nucl Med. .

Abstract

Radiation therapy (RT) is a pillar of cancer therapy used by more than half of all cancer patients. Clinically, RT is mostly delivered as external beam radiation therapy (EBRT). However, the scope of EBRT is limited in the metastatic setting, where all sites of disease need to be irradiated. Such a limitation is attributed to radiation-induced toxicities, for example on bone marrow and hematologic toxicities, resulting from a large EBRT field. Radiopharmaceutical therapy (RPT) has emerged as an alternative to EBRT for the irradiation of all sites of metastatic disease. While RPT can reduce tumor burden, it can also impact the immune system and anti-tumor immunity. Understanding these effects is crucial for predicting and managing treatment-related hematological toxicities and optimizing their integration with other therapeutic modalities, such as immunotherapies. Here, we review the immunomodulatory effects of α- and β-particle emitter-based RPT on various immune cell lines, such as CD8+ and CD4+ T cells, natural killer (NK) cells, and regulatory T (Treg) cells. We briefly discuss Auger electron-emitter (AEE)-based RPT, and finally, we highlight the combination of RPT with immune checkpoint inhibitors, which may offer potential therapeutic synergies for patients with metastatic cancers.

Keywords: alpha-particle emitter; auger electron emitter; beta-particle emitter; immune system; metastatic cancer; radiation therapy; radionuclide; radiopharmaceutical therapy.

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Conflict of interest statement

RH received patent royalties from the Wisconsin Alumni Research Foundation and consulting fees from Archeus Technologies Inc. and Monopar Therapeutics. ZSM is a member of the Scientific Advisory Board for Archeus Technologies, Seneca Therapeutics, and NorthStar Medical Isotopes; received royalties from patents held by the Wisconsin Alumni Research Foundation; received stock/stock options from the Archeus Technologies Scientific Advisory Board and the Seneca Therapeutics Scientific Advisory Board; received research support from Point Biopharma, Telix Pharmaceuticals, and XRD Therapeutics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest. The author(s) declared that they were editorial board members of Frontiers at the time of submission. This had no impact on the peer review process and the final decision.

Figures

Figure 1
Figure 1
Radiopharmaceutical therapy delivers radiation to all sites of disease with potentially less toxicity compared to external beam radiation therapy in widely metastatic disease. (A) To irradiate all sites of disease in patients with widely metastatic disease, including microscopic disease using EBRT, a large radiation field is needed, thus increasing the risk of toxicity. (B) In contrast to EBRT, due to the molecular targeting in RPT, radiation is delivered to malignant cells expressing the target, while irradiation to healthy tissue is minimized due to the differential expression of the target. Made with Biorender.com.
Figure 2
Figure 2
Pharmacophoric model of a radiopharmaceutical agent. The therapeutic effect of a radiopharmaceutical is impacted by the properties of the various domains of the pharmacophoric model, including the radionuclide, chelating agent, linker, and targeting molecule or moiety. Made with Biorender.com.
Figure 3
Figure 3
Systemic radiopharmaceutical treatment may have direct and indirect effects on the tumor microenvironment and immune cells. Preclinical data suggests that RPT with α-particles or β-particles has an immunostimulatory effect, such as an increase in type 1 interferon response, a decrease in regulatory T cells (Tregs), and an increase in immunogenic cell death.
See this image and copyright information in PMC

References

    1. Rupnow BA, Murtha AD, Alarcon RM, Giaccia AJ, Knox SJ. Direct evidence that apoptosis enhances tumor responses to fractionated radiotherapy. Cancer Res. (1998) 58:1779–84. - PubMed
    1. Dewey WC, Ling CC, Meyn RE. Radiation-induced apoptosis: relevance to radiotherapy. Int J Radiat Oncol Biol Phys. (1995) 33:781–96. 10.1016/0360-3016(95)00214-8 - DOI - PubMed
    1. Eriksson D, Stigbrand T. Radiation-induced cell death mechanisms. Tumour Biol. (2010) 31:363–72. 10.1007/s13277-010-0042-8 - DOI - PubMed
    1. Merrick A, Errington F, Milward K, O’Donnell D, Harrington K, Bateman A, et al. Immunosuppressive effects of radiation on human dendritic cells: reduced IL-12 production on activation and impairment of naive T-cell priming. Br J Cancer. (2005) 92(8):1450–8. 10.1038/sj.bjc.6602518 - DOI - PMC - PubMed
    1. McMahon RA, D’Souza C, Neeson PJ, Siva S. Innate immunity: looking beyond T-cells in radiation and immunotherapy combinations. Neoplasia. (2023) 46:100940. 10.1016/j.neo.2023.100940 - DOI - PMC - PubMed

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