Molecular mechanism of bystander effects and related abscopal/cohort effects in cancer therapy

Rong Wang, Tingyang Zhou, Wei Liu and Li Zuo _

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Oncotarget. 2018; 9:18637-18647. https://doi.org/10.18632/oncotarget.24746

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Rong Wang1,2,*, Tingyang Zhou2,3,*, Wei Liu4 and Li Zuo2,3

1Department of Radiation, Fifth People's Hospital of Qinghai Province, Xi Ning, Qing Hai 810007, China

2Radiologic Sciences and Respiratory Therapy Division, School of Health and Rehabilitation Sciences, The Ohio State University College of Medicine, Columbus, Ohio 43210, USA

3Interdisciplinary Biophysics Graduate Program, The Ohio State University, Columbus, Ohio 43210, USA

4Department of Radiation Oncology, Mayo Clinic Arizona, Phoenix, Arizona 85054, USA

*These authors equally contributed to the work

Correspondence to:

Li Zuo, email: [email protected]

Keywords: radiation therapy; non-targeted effects; p53; non-uniform irradiation; reactive oxygen species

Received: December 26, 2017     Accepted: February 25, 2018     Published: April 06, 2018


Cancer cells subjected to ionizing radiation may release signals which can influence nearby non-irradiated cells, termed bystander effects. The transmission of bystander effects among cancer cells involves the activation of inflammatory cytokines, death ligands, and reactive oxygen/nitrogen species. In addition to bystander effects, two other forms of non-target effects (NTEs) have been identified in radiotherapy, as one is called cohort effects and the other is called abscopal effects. Cohort effects represent the phenomenon where irradiated cells can produce signals that reduce the survival of neighboring cells within an irradiated volume. The effects suggest the importance of cellular communication under irradiation with non-uniform dose distribution. In contrast, abscopal effects describe the NTEs that typically occur in non-irradiated cells distant from an irradiated target. These effects can be mediated primarily by immune cells such as T cells. Clinical trials have shown that application of radiation along with immunotherapy may enhance abscopal effects and improve therapeutic efficacy on non-target lesions outside an irradiated field. According to NTEs, cell viability is reduced not only by direct irradiation effects, but also due to signals emitted from nearby irradiated cells. A clinical consideration of NTEs could have a revolutionary impact on current radiotherapy via the establishment of more efficient and less toxic radiobiological models for treatment planning compared to conventional models. Thus, we will review the most updated findings about these effects and outline their mechanisms and potential applications in cancer treatment with a special focus on the brain, lung, and breast cancers.

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