Irradiated tumour cell-derived microparticles upregulate MHC-I expression in cancer cells via DNA double-strand break repair pathway.
Cancer Lett
; 592: 216898, 2024 Jun 28.
Article
en En
| MEDLINE
| ID: mdl-38670306
ABSTRACT
Radiotherapy (RT) is used for over 50 % of cancer patients and can promote adaptive immunity against tumour antigens. However, the underlying mechanisms remain unclear. Here, we discovered that RT induces the release of irradiated tumour cell-derived microparticles (RT-MPs), which significantly upregulate MHC-I expression on the membranes of non-irradiated cells, enhancing the recognition and killing of these cells by T cells. Mechanistically, RT-MPs induce DNA double-strand breaks (DSB) in tumour cells, activating the ATM/ATR/CHK1-mediated DNA repair signalling pathway, and upregulating MHC-I expression. Inhibition of ATM/ATR/CHK1 reversed RT-MP-induced upregulation of MHC-I. Furthermore, phosphorylation of STAT1/3 following the activation of ATM/ATR/CHK1 is indispensable for the DSB-dependent upregulation of MHC-I. Therefore, our findings reveal the role of RT-MP-induced DSBs and the subsequent DNA repair signalling pathway in MHC-I expression and provide mechanistic insights into the regulation of MHC-I expression after DSBs.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Antígenos de Histocompatibilidad Clase I
/
Transducción de Señal
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Regulación hacia Arriba
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Reparación del ADN
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Roturas del ADN de Doble Cadena
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Micropartículas Derivadas de Células
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Proteínas de la Ataxia Telangiectasia Mutada
Límite:
Animals
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Humans
Idioma:
En
Revista:
Cancer Lett
/
Cancer lett
/
Cancer letters
Año:
2024
Tipo del documento:
Article