Novel combination of radiotherapy and immunotherapy enhances antitumor response in animal models of breast cancer

Researchers of the Combined Translational Immunotherapy Strategiesgroup of the Cimaintegrated in the Cancer Center Clínica Universidad de Navarra, have developed a novel combination of radiotherapy and immunotherapy that improves the antitumor response in animal models of breast cancer.

Radiotherapy is an effective and widely used therapeutic tool in the treatment of cancer for more than a century. It plays a crucial role in eradicating tumors and improving patients' quality of life. 

"Although traditionally known for its ability to destroy tumor cells, it has recently gained attention for its ability to modify the tumor microenvironment and enhance immune responses. In this study we have further explored this potential and found that radiotherapy is an immunomodulatory tool in the treatment of cancer," explains Dr. María Rodríguez-Ruiz. Dr. María Rodríguez-Ruizspecialist in Radiation Oncology at the Cancer Center Clínica Universidad de Navarra co-director of the study. and co-director of the study.

The work, published in Journal for Immunotherapy of Cancerhas combined radiotherapy with an innovative immunotherapy treatment (an antibody targeting the FAP protein, which is present on cells in the tumor microenvironment). "This molecule (muFAP-4-1BBL) demonstrates excellent local and distant tumor control when combined with localized radiotherapy. In particular, it improves the immune response and offers a better therapeutic response than if it is administered individually," explains Eneko Garate, a predoctoral student at Cima and first author of the work.

Promising combination for primary and distant tumors

The researchers have observed that this combination not only controls the primary tumor, but also generates effects on distant, non-irradiated tumors, improving treatment efficacy. "Moreover, adding immune checkpoint inhibitors such as PD-1 and CTLA-4 synergistically enhances the antitumor immune response. The experimental treatment takes advantage of the induction of fibrosis (scarring) by radiotherapy to direct a potent immunostimulatory drug to the irradiated tumor tissue," explains Dr. Ignacio Melero. Dr. Ignacio Meleroco-director of the Immunology and Immunotherapy Program of the Cima and of the Clínica Universidad de Navarra and co-director of the study.

Radiotherapy not only acts directly on the tumor, but also creates a more favorable environment for immunotherapy. "Our research has shown thatby taking advantage of this immunomodulatory effect of radiotherapy, we can significantly improve the immune response and tumor control," comments Dr. Rodriguez.

Pharmaceutical innovation for the benefit of the patient

"The findings of this study provide a solid basis for moving toward clinical trials, bringing us closer to a new era of personalized treatments that take advantage of synergies between radiotherapy and immunotherapy and reduce side effects for patients," the scientists say. 

The work has been supported by the imCORE research network , the CRIS Foundation against Cancer, the Spanish association Against Cancer and its headquarters in Navarra.

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J Immunother Cancer. 2025 Feb 11;13(2):e009852. doi: 10.1136/jitc-2024-009852.