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Harnessing the Power of Radiotherapy to Boost Immunotherapy – Gustave Roussy Research

POEM Group

Mar 22, 2025, 05:32

Harnessing the Power of Radiotherapy to Boost Immunotherapy – Gustave Roussy Research

Gustave Roussy Research posted on LinkedIn:

“Harnessing the Power of Radiotherapy to Boost Immunotherapy. A groundbreaking study in Cancer Cell explores how low-dose irradiation of the gut (ILDR) enhances the efficacy of PD-L1 blockade in metastatic cancer patients, shedding light on a novel synergy between radiation therapy and immune checkpoint blockade.

The Context:

Radiation therapy (RT) has long been used to shrink tumors, but emerging evidence suggests that it does more than just kill cancer cells—it can also stimulate the immune system. When combined with immune checkpoint blockade (ICB), RT has been shown to elicit both local and systemic anti-tumor responses, a phenomenon known as the abscopal effect. However, not all patients benefit from this synergy, and the underlying mechanisms remain poorly understood.

The Study and Key Findings:

Researchers from Gustave Roussy and collaborators investigated whether off-target low-dose irradiation of the gut (ILDR) could improve the response to PD-L1 blockade. Their work, spanning eight retrospective studies and a phase 2 clinical trial, revealed that:

ILDR enhances the systemic immune response, increasing the chances of eradicating non-irradiated tumors (abscopal effect).
This effect is dose-dependent (optimal range: 1–3 Gy) and influenced by gut microbiota composition.
Christensenellaceae bacteria were identified as key players in boosting the anti-tumor effects of ILDR + PD-L1 blockade.
ILDR facilitates the migration of PD-L1+ dendritic cells from the gut to tumor-draining lymph nodes, improving immune activation.
A phase 2 trial confirmed that ILDR helps overcome resistance to PD-1 blockade, offering new hope for patients who had stopped responding to immunotherapy.

Why It Matters:

This study highlights a novel radiotherapy-microbiota-immunotherapy axis, showing that targeted low-dose irradiation could serve as a powerful immune modulator. Understanding this interplay opens new avenues for personalized cancer treatment, where radiotherapy is not just a local intervention but an integral part of systemic immune activation.”

Immunotherapy