Radiotherapy-Associated Systemic Antitumor Responses Beyond the Classical Abscopal Paradigm.

Area of Science:

• Oncology
• Immunology
• Radiation Oncology

Background:

• Radiotherapy (RT) is traditionally local, but systemic effects are increasingly recognized.
• The abscopal effect, regression of distant tumors post-RT, is gaining attention with immune checkpoint inhibitors (ICIs).
• RT may enhance systemic antitumor immunity via immunogenic cell death and immune activation.

Purpose of the Study:

• To review clinical evidence and biological mechanisms of radiation-associated systemic antitumor responses.
• To discuss emerging concepts beyond the RT-immunotherapy paradigm.
• To identify challenges and propose a "beyond-abscopal" framework.

Main Methods:

• Literature review of preclinical and clinical studies.
• Analysis of mechanisms involving innate and adaptive immunity, and tumor microenvironment.
• Examination of systemic responses in various treatment settings.

Main Results:

• Abscopal responses are rare and heterogeneous, with mechanisms not fully understood.
• RT alone, chemotherapy, and CNS therapies can induce systemic tumor regression.
• Overlapping immunologic mechanisms contribute to radiation-associated systemic responses.

Conclusions:

• Systemic antitumor effects of RT are mediated by complex immunologic interactions.
• The "beyond-abscopal" concept offers a framework for future research.
• Further validation and biomarker development are crucial for clinical translation.