PD-1 Restrains Radiotherapy-Induced Abscopal Effect

Area of Science:

• Immunology
• Oncology
• Radiotherapy

Background:

• Programmed cell death protein 1 (PD-1) plays a role in immune regulation.
• Stereotactic ablative radiotherapy (SABR) can induce systemic antitumor immune responses.
• The abscopal effect, a rare phenomenon where radiation of a tumor leads to regression of distant tumors, is not fully understood.

Purpose of the Study:

• To investigate the influence of PD-1 expression on the abscopal effect induced by SABR.
• To evaluate the efficacy of combining SABR with PD-1 blockade as an immunotherapy strategy.

Main Methods:

• Comparison of SABR efficacy in PD-1-expressing wild-type (WT) and PD-1-deficient knockout (KO) mice.
• Administration of PD-1-blocking antibody in WT mice.
• Assessment of tumor regression, survival rates, and immune cell phenotypes (CD11a(high) CD8(+) T-cells).

Main Results:

• PD-1 expression compromised survival in SABR-treated mice.
• PD-1 blockade in WT mice mimicked the enhanced survival and antitumor responses seen in PD-1 KO mice.
• The combination of SABR and PD-1 blockade resulted in synergistic primary tumor regression and a significant abscopal effect (66% reduction in non-irradiated tumor size).
• A tumor-specific immune response mediated by CD11a(high) CD8(+) T-cells was associated with SABR efficacy.

Conclusions:

• SABR induces a tumor-specific abscopal immune response that is potentiated by PD-1 blockade.
• The combination of SABR and PD-1 blockade demonstrates significant therapeutic potential for managing metastatic cancer.