Background
Chemotherapeutics can stimulate immune antitumor response by inducing immunogenic cell death (ICD), which is characterized by the appearance of Damage-Associated Molecular Patterns (DAMPs) like the exposure of calreticulin (CRT) in cell surface, the release of ATP and the secretion of High Mobility Group Box 1 (HMGB1).
Methods
Here, our objective was to investigate levels of ICD-associated DAMPs induced by chemotherapeutics commonly used in the clinical practice of non-small cell lung cancer (NSCLC) and the prognosis values of these DAMPs.A549 human lung adenocarcinoma cells were treated with cisplatin, carboplatin, etoposide, paclitaxel and gemcitabine using clinically relevant conditions (doses, times and co-treatments). We assessed ICD-associated DAMPs, cell viability, apoptosis and autophagy in an integrated way.
Results
We found that cisplatin induced the highest levels of apoptosis, while carboplatin and etoposide were the less cytotoxic. Cisplatin also induced the highest levels of ICD-associated DAMPs, which was not incremented by co-treatments. Etoposide induced the lower levels of ICD and the highest levels of autophagy, suggesting that the cytoprotective role of autophagy is dominant in relation to its pro-ICD role. High levels of CRT were associated with better prognosis in TCGA databank. In an integrative analysis we found a strong negative correlation between cell number and ICD-associated DAMPs as well as between autophagy and ICD-associated DAMPs. We also purpose a mathematical integration of ICD-associated DAMPs in an index (InDAMPs) that may represent with greater biological relevance this process.
Conclusions
Cisplatin alone induced the highest levels of ICD-associated DAMPs, so that its combination with immunotherapies can be a promising therapeutic strategy in NSCLC.
como la calidad de las instalaciones e infraestructura, la presencia y calidad de programas de capacitación, el apoyo de las autoridades del hospital, la aceptabilidad de los servicios por otros profesionales de la salud, el clima laboral y la satisfacción de los recursos humanos. ConClusiones: El marco conceptual desarrollado permite fundamentar la evaluación de la calidad de SMF's. El abordaje cualitativo realizado permitió identificar aspectos clave en las dimensiones de calidad.
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