Low-dose radiotherapy enhances the efficacy of PD-L1 blockade and induces the abscopal effect

作者：Pierre-Antoine Laurent, Shi Liu, Lisa Bouarroudj, Nathan Benzazon, Marine Gerbé de Thoré, Winchygn Liu, Marine Aglave, Paul Bergeron, Flavie Naulin, Lisa Sitterlé, Daphné Morel, Antonin Lévy, Céline Clémenson, Michele Mondini, Charlotte Robert, Lydia Meziani, Eric C Deutsch · 发表于：Journal for ImmunoTherapy of Cancer · 年份：2025 · 被引用次数：13 · 研究领域：Immune cells in cancer、Cancer Immunotherapy and Biomarkers、Cancer Cells and Metastasis

Background Low-dose radiotherapy (RT) is a promising treatment likely to increase the efficacy of immunotherapy, including programmed cell death ligand 1 (PD-L1) blockade, in cancer therapy. Further exploration and optimization of such combinatorial strategies are required. Notably, the ability of low-dose RT to enhance the efficacy of immune-checkpoint inhibitors (ICI) in distant, unirradiated tumors is debated. Methods We used a stepwise preclinical approach in immunocompetent mice bearing different murine tumor models (MC38 or CT26), with one or two tumors per mouse. Mice received tumor-only irradiation consisting of either low-dose RT (2x0.5 Gy to 2x2 Gy) or high-dose RT (2x6 Gy to 2x8 Gy) combined with anti-PD-L1. Tumor growth rate and survival were compared across the different conditions. The immune microenvironments of both irradiated and distant unirradiated tumors were characterized using single-cell RNA sequencing. Results We first demonstrated that low-dose RT 2×2 Gy combined with anti-PD-L1 is as effective as high-dose RT 2×6 Gy in delaying the growth of irradiated tumors. Subsequently, we showed that low-dose RT to one tumor enhances the efficacy of anti-PD-L1 consolidation therapy in a distant, unirradiated tumor, thereby inducing an abscopal effect comparable to that observed with high-dose RT. Single-cell RNA sequencing analysis highlighted the polarization of tumor-associated macrophages (TAMs) within distant unirradiated tumors towards a pro-inflammatory ph...