Radiotherapy and Immune Response: the Systemic Effects of a Local Treatment

Overview

Journal Clinics (Sao Paulo)

Publisher Elsevier

Specialty General Medicine

Date 2018 Dec 13

PMID 30540123

Citations 108

Authors

Heloisa de Andrade Carvalho

Rosangela Correa Villar

Affiliations

Soon will be listed here.

Abstract

Technological developments have allowed improvements in radiotherapy delivery, with higher precision and better sparing of normal tissue. For many years, it has been well known that ionizing radiation has not only local action but also systemic effects by triggering many molecular signaling pathways. There is still a lack of knowledge of this issue. This review focuses on the current literature about the effects of ionizing radiation on the immune system, either suppressing or stimulating the host reactions against the tumor, and the factors that interact with these responses, such as the radiation dose and dose / fraction effects in the tumor microenvironment and vasculature. In addition, some implications of these effects in cancer treatment, mainly in combined strategies, are addressed from the perspective of their interactions with the more advanced technology currently available, such as heavy ion therapy and nanotechnology.

Citing Articles

The Histomorphology to Molecular Transition: Exploring the Genomic Landscape of Poorly Differentiated Epithelial Endometrial Cancers.

Molefi T, Mabonga L, Hull R, Mwazha A, Sebitloane M, Dlamini Z Cells. 2025; 14(5).

PMID: 40072110 PMC: 11898822. DOI: 10.3390/cells14050382.

Neoadjuvant chemoradiotherapy up-regulates PD-L1 in radioresistant colorectal cancer.

Bae S, Lee H, Park J, Seo I, Cho J, Kim J Clin Transl Radiat Oncol. 2025; 51():100906.

PMID: 39811542 PMC: 11732604. DOI: 10.1016/j.ctro.2024.100906.

Distribution of metastases after radiotherapy in relation to radiation exposure fields: evaluation by F-FDG PET/CT.

Liang J, Li W, Zhang R, Li W, Lin P, Nie H Sci Rep. 2024; 14(1):29816.

PMID: 39616185 PMC: 11608237. DOI: 10.1038/s41598-024-81303-3.

Results of an Integrated Phase I/II Prospective Clinical Trial (NEXIS) for Neoadjuvant Anti-PD-L1 (Durvalumab) and Anti-CTLA-4 (Tremelimumab) With Radiation for High-Risk Soft-Tissue Sarcoma of the Trunk and Extremities.

Ng V, Sahlani M, Fogel J, Chiu A, Kallen M, Davis D Cureus. 2024; 16(10):e72119.

PMID: 39575028 PMC: 11581454. DOI: 10.7759/cureus.72119.

Hypofractionated radiotherapy with simultaneous integrated boost for localized prostate cancer patients: effects on immune system and prediction of toxicity.

DAuria F, Valvano L, Calice G, DEsposito V, Cabaro S, Formisano P Front Immunol. 2024; 15:1457839.

PMID: 39530099 PMC: 11550950. DOI: 10.3389/fimmu.2024.1457839.

References

Formenti S, Demaria S . Systemic effects of local radiotherapy. Lancet Oncol. 2009; 10(7):718-26. PMC: 2782943. DOI: 10.1016/S1470-2045(09)70082-8. View

Levy A, Chargari C, Marabelle A, Perfettini J, Magne N, Deutsch E . Can immunostimulatory agents enhance the abscopal effect of radiotherapy?. Eur J Cancer. 2016; 62:36-45. DOI: 10.1016/j.ejca.2016.03.067. View

Schaue D, Comin-Anduix B, Ribas A, Zhang L, Goodglick L, Sayre J . T-cell responses to survivin in cancer patients undergoing radiation therapy. Clin Cancer Res. 2008; 14(15):4883-90. PMC: 2748652. DOI: 10.1158/1078-0432.CCR-07-4462. View

Sanzari J, Wan X, Muehlmatt A, Lin L, Kennedy A . Comparison of changes over time in leukocyte counts in Yucatan minipigs irradiated with simulated solar particle event-like radiation. Life Sci Space Res (Amst). 2015; 4:11-6. PMC: 4356949. DOI: 10.1016/j.lssr.2014.12.002. View

Williams G . Programmed cell death: apoptosis and oncogenesis. Cell. 1991; 65(7):1097-8. DOI: 10.1016/0092-8674(91)90002-g. View

Sanzari J, Cengel K, Wan X, Rusek A, Kennedy A . Acute Hematological Effects in Mice Exposed to the Expected Doses, Dose-rates, and Energies of Solar Particle Event-like Proton Radiation. Life Sci Space Res (Amst). 2014; 2:86-91. PMC: 4155507. DOI: 10.1016/j.lssr.2014.01.003. View

Dunn G, Old L, Schreiber R . The three Es of cancer immunoediting. Annu Rev Immunol. 2004; 22:329-60. DOI: 10.1146/annurev.immunol.22.012703.104803. View

Kang J, Demaria S, Formenti S . Current clinical trials testing the combination of immunotherapy with radiotherapy. J Immunother Cancer. 2016; 4:51. PMC: 5028964. DOI: 10.1186/s40425-016-0156-7. View

Rodel F, Frey B, Multhoff G, Gaipl U . Contribution of the immune system to bystander and non-targeted effects of ionizing radiation. Cancer Lett. 2013; 356(1):105-13. DOI: 10.1016/j.canlet.2013.09.015. View

10.

Eriksson D, Stigbrand T . Radiation-induced cell death mechanisms. Tumour Biol. 2010; 31(4):363-72. DOI: 10.1007/s13277-010-0042-8. View

11.

Gridley D, Obenaus A, Bateman T, Pecaut M . Long-term changes in rat hematopoietic and other physiological systems after high-energy iron ion irradiation. Int J Radiat Biol. 2008; 84(7):549-59. DOI: 10.1080/09553000802203614. View

12.

Nesslinger N, Sahota R, Stone B, Johnson K, Chima N, King C . Standard treatments induce antigen-specific immune responses in prostate cancer. Clin Cancer Res. 2007; 13(5):1493-502. DOI: 10.1158/1078-0432.CCR-06-1772. View

13.

Karam S, Bhatia S . The radiobiological targets of SBRT: tumor cells or endothelial cells?. Ann Transl Med. 2015; 3(19):290. PMC: 4671867. DOI: 10.3978/j.issn.2305-5839.2015.09.17. View

14.

Fuks Z, Kolesnick R . Engaging the vascular component of the tumor response. Cancer Cell. 2005; 8(2):89-91. DOI: 10.1016/j.ccr.2005.07.014. View

15.

Schweitzer A, Revskaya E, Chu P, Pazo V, Friedman M, Nosanchuk J . Melanin-covered nanoparticles for protection of bone marrow during radiation therapy of cancer. Int J Radiat Oncol Biol Phys. 2010; 78(5):1494-502. PMC: 3001108. DOI: 10.1016/j.ijrobp.2010.02.020. View

16.

Dunn G, Bruce A, Ikeda H, Old L, Schreiber R . Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol. 2002; 3(11):991-8. DOI: 10.1038/ni1102-991. View

17.

Garcia-Barros M, Paris F, Cordon-Cardo C, Lyden D, Rafii S, Haimovitz-Friedman A . Tumor response to radiotherapy regulated by endothelial cell apoptosis. Science. 2003; 300(5622):1155-9. DOI: 10.1126/science.1082504. View

18.

Paris F, Fuks Z, Kang A, Capodieci P, Juan G, Ehleiter D . Endothelial apoptosis as the primary lesion initiating intestinal radiation damage in mice. Science. 2001; 293(5528):293-7. DOI: 10.1126/science.1060191. View

19.

Gallo P, Gallucci S . The dendritic cell response to classic, emerging, and homeostatic danger signals. Implications for autoimmunity. Front Immunol. 2013; 4:138. PMC: 3677085. DOI: 10.3389/fimmu.2013.00138. View

20.

Timmerman R, Herman J, Cho L . Emergence of stereotactic body radiation therapy and its impact on current and future clinical practice. J Clin Oncol. 2014; 32(26):2847-54. PMC: 4152712. DOI: 10.1200/JCO.2014.55.4675. View