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Genomic profiling by SNParray of human sarcomas developed in the field of irradiation after radiotherapy

ABSTRACT: Genomic signature of the ionizing radiation effect in sarcomas developed in the field of irradiation after radiotherapy

ORGANISM(S): Homo sapiens

DISEASE(S): angiosarcoma

SUBMITTER: Nabila Hadj-Hamou

PROVIDER: E-MEXP-3248 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Transcription profiling by array of human sarcomas developed in the field of irradiation after radiotherapy.

Project description:Transcriptome signature of the ionizing radiation effect in sarcomas developed in the field of irradiation after radiotherapy

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Genomic profiling by SNParray of human angiosarcomas

Project description:Genomic signature of the ionizing radiation effect in angiosarcoma developed in the field of irradiation after radiotherapy

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Project description:Abstract: Despite impressive responses in some patients, immunotherapy fails to cure most cancer patients. Preclinical studies indicate that radiotherapy synergizes with immunotherapy, promoting radiation-induced antitumor immunity. Nearly all preclinical immunotherapy studies utilize transplant tumor models, but cure rates of transplant tumors treated with immunotherapy overestimate patient responses. Here, we show that transplant sarcomas are cured by PD-1 blockade and radiotherapy, but identical treatment fails in autochthonous sarcomas, which demonstrate tumor-specific immune tolerance. We characterize tumor-infiltrating immune cells from transplant and primary tumors and reveal striking differences in their immune landscapes. Although radiotherapy remodels myeloid cells in primary and transplant sarcomas, only transplant tumors are enriched for activated CD8+ T cells associated with tumor clearance. By CIBERSORTx, the immune microenvironment of primary sarcomas in mice transcriptionally resembles most human sarcomas, while transplant sarcomas model the most inflamed sarcomas in patients. These results identify distinct microenvironments in murine sarcomas that coevolve with the immune system and suggest that patients whose sarcomas have an immune phenotype similar to transplant tumors may benefit most from PD-1 blockade and radiotherapy.

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Project description:Abstract: Immunotherapy fails to cure most cancer patients. Preclinical studies indicate that radiotherapy synergizes with immunotherapy, promoting radiation-induced antitumor immunity. Most preclinical immunotherapy studies utilize transplant tumor models, which overestimate patient responses. Here, we show that transplant sarcomas are cured by PD-1 blockade and radiotherapy, but identical treatment fails in autochthonous sarcomas, which demonstrate immunoediting, decreased neoantigen expression, and tumor-specific immune tolerance. We characterize tumor-infiltrating immune cells from transplant and primary tumors, revealing striking differences in their immune landscapes. Although radiotherapy remodels myeloid cells in both models, only transplant tumors are enriched for activated CD8+ T cells. The immune microenvironment of primary murine sarcomas resembles most human sarcomas, while transplant sarcomas resemble the most inflamed human sarcomas. These results identify distinct microenvironments in murine sarcomas that coevolve with the immune system and suggest that patients with a sarcoma immune phenotype similar to transplant tumors may benefit most from PD-1 blockade and radiotherapy.

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Radiation exposure of mouse embryonic brain - 2 h, 24 h post-irradiation

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Gene expression profiles of primary tumors with radiotherapy and lung metastases in mouse squamous cell carcinoma model.

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