Oncology research · 2025
Preventive effects of low-dose radiation and hypofractionated radiation plus anti-programmed cell death protein 1 on lung metastasis in breast cancer.
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Münchau A, Bahlke G, Allen P J, Quinn N P, Lees A J, Rothwell J C, Palmer J D, Bhatia K P
Аннотация
BACKGROUND: Previous experiments have demonstrated that hypofractionated radiation therapy (HFRT), low-dose radiation therapy (LDRT), and combined anti-programmed cell death protein 1 (αPD-1) can enhance the abscopal effect. Combined with the phenomenon of low prognosis in patients with breast cancer lung metastasis, our study establishes a mouse model and changes the irradiation regimen of LDRT to explore its preventive effect on breast cancer lung metastasis.
METHODS: The breast cancer subcutaneous graft tumor model was developed. Two-lung prophylactic LDRT was performed prior to the onset of lung metastases, in combination with HFRT (8 Gy, 3f), and αPD-1 (200 μg, 4f) therapy. We watched and documented the tumor volume, survival duration, and number of lung metastases. Furthermore, after labeling the corresponding cells using markers, we detected immune-related cell infiltration by immunohistochemistry and flow cytometry, such as T cells. We also determined the expression of cytokines (IFN-γ and TNF-α) by enzyme-linked immunosorbent assay.
RESULT: The triple therapy (HFRT+LDRT+αPD-1) resulted in tumor shrinkage and prolonged survival in mice, with median survival extending from 35 to 52 days. The most notable decrease in the quantity of advanced lung metastatic nodules in breast cancer was observed with the triple therapy (HFRT+LDRT+αPD-1) (p < 0.05). Furthermore, according to immunohistochemistry and flow cytometry, the triple treatment (HFRT+LDRT+αPD-1) showed the greatest expression of CD8+ T cells. Additionally, the ratio of CD8+/CD4+ T cells was considerably greater than that of the groups (p < 0.0001). Triple therapy (HFRT+LDRT+αPD-1) increased the recruitment of DCs cells, promoted IFN-γ and TNF-α expression, and curbed the aggregation of MDSCs cells (p < 0.05).
CONCLUSION: Prophylactic LDRT to the lungs, based on HFRT and αPD-1, can enhance anti-tumor efficacy and prevent advanced lung metastases from breast cancer. The process involves boosting the recruitment of DCs and CD8+ T cells, preventing MDSC cell aggregation, and lessening the tumor microenvironment's immunosuppressive effects.
METHODS: The breast cancer subcutaneous graft tumor model was developed. Two-lung prophylactic LDRT was performed prior to the onset of lung metastases, in combination with HFRT (8 Gy, 3f), and αPD-1 (200 μg, 4f) therapy. We watched and documented the tumor volume, survival duration, and number of lung metastases. Furthermore, after labeling the corresponding cells using markers, we detected immune-related cell infiltration by immunohistochemistry and flow cytometry, such as T cells. We also determined the expression of cytokines (IFN-γ and TNF-α) by enzyme-linked immunosorbent assay.
RESULT: The triple therapy (HFRT+LDRT+αPD-1) resulted in tumor shrinkage and prolonged survival in mice, with median survival extending from 35 to 52 days. The most notable decrease in the quantity of advanced lung metastatic nodules in breast cancer was observed with the triple therapy (HFRT+LDRT+αPD-1) (p < 0.05). Furthermore, according to immunohistochemistry and flow cytometry, the triple treatment (HFRT+LDRT+αPD-1) showed the greatest expression of CD8+ T cells. Additionally, the ratio of CD8+/CD4+ T cells was considerably greater than that of the groups (p < 0.0001). Triple therapy (HFRT+LDRT+αPD-1) increased the recruitment of DCs cells, promoted IFN-γ and TNF-α expression, and curbed the aggregation of MDSCs cells (p < 0.05).
CONCLUSION: Prophylactic LDRT to the lungs, based on HFRT and αPD-1, can enhance anti-tumor efficacy and prevent advanced lung metastases from breast cancer. The process involves boosting the recruitment of DCs and CD8+ T cells, preventing MDSC cell aggregation, and lessening the tumor microenvironment's immunosuppressive effects.