Background: Chemotherapeutics can stimulate immune antitumor response by inducing immunogenic cell death (ICD), which is activated by Damage-Associated Molecular Patterns (DAMPs) like the exposure of calreticulin (CRT) on the cell surface, the release of ATP and the secretion of High Mobility Group Box 1 (HMGB1). Methods: Here, we investigated the levels of ICD-associated DAMPs induced by chemotherapeutics commonly used in the clinical practice of non-small cell lung cancer (NSCLC) and the association of these DAMPs with apoptosis and autophagy. A549 human lung adenocarcinoma cells were treated with clinically relevant doses of cisplatin, carboplatin, etoposide, paclitaxel and gemcitabine. We assessed ICD-associated DAMPs, cell viability, apoptosis and autophagy in an integrated way. Results: Cisplatin and its combination with etoposide induced the highest levels of apoptosis, while etoposide was the less pro-apoptotic treatment. 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 positive correlation between DAMPs and apoptosis, and a negative correlation between cell number and ICD-associated DAMPs as well as between autophagy and apoptosis markers. We also purpose a mathematical integration of ICDassociated DAMPs in an index (IndImunnog) that may represent with greater biological relevance this process. Cisplatin-treated cells showed the highest IndImmunog, while etoposide was the less immunogenic and the more pro-autophagic treatment.

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.