Combining radiotherapy and cancer immunotherapy: a paradigm shift

Area of Science:

• Oncology
• Immunology
• Radiation Oncology

Background:

• Therapeutic ionizing radiation (radiotherapy) traditionally targets tumors via cytocidal effects.
• Its role in improving cancer patient survival is mainly attributed to local tumor control and reduced systemic spread.
• Emerging evidence suggests radiotherapy also stimulates systemic antitumor immunity.

Purpose of the Study:

• To propose a paradigm shift in understanding radiotherapy's effects, recognizing its role as a systemic immune adjuvant.
• To highlight the potential of combining radiotherapy with immunotherapy for metastatic cancer.
• To summarize evidence supporting radiotherapy as an immune adjuvant and discuss challenges.

Main Methods:

• Review of experimental data from multiple cancer models.
• Analysis of clinical outcomes from combining radiotherapy with immunotherapy in metastatic patients.
• Critical appraisal of current knowledge on radiotherapy's immunomodulatory effects.

Main Results:

• Experimental data support radiotherapy's role in inducing systemic antitumor immunity.
• Clinical responses observed in metastatic cancer patients treated with radiotherapy plus immunotherapy.
• Radiotherapy is evolving from a palliative treatment to a potent immunotherapy adjuvant.

Conclusions:

• Radiotherapy can act as an immune adjuvant, enhancing systemic antitumor responses.
• Combining radiotherapy with immunotherapy offers a novel strategy to extend survival in advanced cancer.
• Challenges remain in translating these findings, including understanding potential immunosuppressive effects of radiation.