Effects of prior irradiation on the microenvironment of a radiation-associated breast cancer model increase sensitivity to immune checkpoint inhibition.

Authors

Md Mahfuzur Rahman, Tracy J Berg, Raad H Allawi, Jen Zaborek, Paul A Clark, Zachary S Morris

Published in

International journal of radiation oncology, biology, physics. Oct 14, 2026. Epub Oct 14, 2026.

Abstract

Radiotherapy confers a later risk of secondary malignancies, including radiation-associated breast cancer. Distinctive molecular profiles emerge in tumors from pre-irradiated tumor beds, but effects on therapeutic options remain understudied.
We developed a murine model of radiation-associated breast cancer by transplanting p53-mutant mammary HC11 epithelial cells that had been previously exposed to radiation (HC11RT) into mammary fat pads (MFP) that had been previously irradiated.
Tumor incidence from HC11RT cells increased two-fold when grown in irradiated MFP. Compared to tumors grown in sham-irradiated MFP, tumors from irradiated MFP had elevated TGFβ in both tumor and CD8⁺ T cells and elevated PD-L1 on CD4⁺ T cells, resulting in improved response to immune checkpoint inhibition (ICI).
This study provides evidence that prior irradiation potentiates tumorigenesis and immune evasion through both tumor cell autonomous and non-autonomous mechanisms. As a result, radiation-associated cancers may exhibit greater response to ICI than tumors of the same histology that are not associated with prior radiotherapy.

PMID:
42874813
Bibliographic data and abstract were imported from PubMed on 15 Oct 2026.

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