PARP inhibitor niraparib as a radiosensitizer promotes antitumor immunity of radiotherapy in EGFR-mutated non-small cell lung cancer
Clin. transl. oncol. (Print)
; 23(9): 1827-1837, sept. 2021. graf
Artigo
em Inglês
| IBECS
| ID: ibc-222182
Biblioteca responsável:
ES1.1
Localização: ES15.1 - BNCS
ABSTRACT
Background Poly-(ADP-Ribose)-Polymerase inhibitors (PARPi) were reported as radiosensitizers in non-small cell lung cancer (NSCLC) with wide-type epidermal growth factor receptor (EGFR), but the effects of radiation combined with PARPi were not investigated in EGFR-mutated NSCLC. Moreover, the underlying mechanisms were not well examined. This study aimed to study the efficacy of radiation combined with niraparib in EGFR-mutated NSCLC and explore their influence on the immune system. Methods Clone formation and apoptosis assay were conducted to explore the effects of niraparib and radiation. Immunofluorescence was conducted to detect the double-strand DNA breaks. Real-time PCR and immunoblotting were employed to evaluate the activation of STING/TBK1/TRF3 pathway and the expression levels of interferon β, CCL5 and CXCL10. Immunocompetent mice model bearing with subcutaneous Lewis lung cancer was established to confirm the results in vivo. Results Niraparib and radiation were synergistic to inhibit tumor both in vitro and in vivo. Radiation plus niraparib could activate anti-tumor immunity, which appeared as increased CD8+ T lymphocytes and activated STING/TBK1/IRF3 pathway. Conclusion PARPi not only as a radiosensitizer inhibited EGFR-mutated NSCLC tumor growth, but also cooperated with radiation to promote anti-tumor immune responses (AU)
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Espanha
Base de dados:
IBECS
Assunto principal:
Radiossensibilizantes
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Carcinoma Pulmonar de Células não Pequenas
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Genes erbB-1
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Quimiorradioterapia
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Neoplasias Pulmonares
Limite:
Humanos
Idioma:
Inglês
Revista:
Clin. transl. oncol. (Print)
Ano de publicação:
2021
Tipo de documento:
Artigo
Instituição/País de afiliação:
Zhongnan Hospital of Wuhan University/China