In recent years, cancer therapies using immune checkpoint inhibitors (ICIs) have achieved meaningful success, with patients with advanced tumors presenting longer survival times and better quality of life. However, several patients still do not exhibit good clinical outcomes for ICI therapy due to low sensitivity. To solve this, researchers have focused on identifying the cellular and molecular mechanisms underlying resistance to ICI therapy. ICI therapy induces apoptosis, which is the most frequent regulated cell death (RCD) but lacks immunogenicity and is regarded as an “immune silent” cell death. Ferroptosis, a unique type of non-apoptotic-RCD, has been preliminarily identified as an immunogenic cell death (ICD), stimulating tumor-antigen-specific immune responses and augmenting anti-tumor immune effects. However, ferroptosis has rarely been used in clinical practice. Present evidence strongly supports that the interferon-γ signaling pathway is at the crossroads of ICI therapy and ferroptosis. TYRO3, a receptor tyrosine kinase, is highly expressed in tumors and can induce anti-programmed cell death (PD)-ligand 1/PD-1 therapy resistance by limiting tumoral ferroptosis. Therefore, in this review, we summarize the clinical practice and effects of ICI therapy in various cancers. We also provide an overview of ferroptosis and report the molecular connections between cancer cell ferroptosis and ICI therapy, and discuss the possibility to reverse ICI therapy resistance by inducing cancer cell ferroptosis.
Aims Acute heart failure (AHF) poses a major threat to hospitalized patients for its high mortality rate and serious complications. The aim of this study is to determine whether hypocapnia [defined as the partial pressure of arterial carbon dioxide (PaCO 2 ) below 35 mmHg] on admission could be associated with in‐hospital all‐cause mortality in AHF. Methods and results A total of 676 patients treated in the coronary care unit for AHF were retrospectively analysed, and the study endpoint was in‐hospital all‐cause mortality. The 1:1 propensity score matching (PSM) analysis, Kaplan–Meier curve, and Cox regression model were used to explore the association between hypocapnia and in‐hospital all‐cause mortality in AHF. Receiver operating characteristic (ROC) curve and Delong's test were used to assess the performance of hypocapnia in predicting in‐hospital all‐cause mortality in AHF. The study cohort included 464 (68.6%) males and 212 (31.4%) females, and the median age was 66 years (interquartile range 56–74 years). Ninety‐eight (14.5%) patients died during hospitalization and presented more hypocapnia than survivors (76.5% vs. 45.5%, P < 0.001). A 1:1 PSM was performed between hypocapnic and non‐hypocapnic patients, with 264 individuals in each of the two groups after matching. Compared with non‐hypocapnic patients, in‐hospital mortality was significantly higher in hypocapnic patients both before (22.2% vs. 6.8%, P < 0.001) and after (20.8% vs. 8.7%, P < 0.001) PSM. Kaplan–Meier curve showed a significantly higher probability of in‐hospital death in patients with hypocapnia before and after PSM (both P < 0.001 for the log‐rank test). Multivariate Cox regression analysis showed that hypocapnia was an independent predictor of AHF mortality both before [hazard ratio (HR) 2.22; 95% confidence interval (CI) 1.23–3.98; P = 0.008] and after (HR 2.19; 95% CI 1.18–4.07; P = 0.013) PSM. Delong's test showed that the area under the ROC curve was improved after adding hypocapnia into the model (0.872, 95% CI 0.839–0.901 vs. 0.855, 95% CI 0.820–0.886, P = 0.028). PaCO 2 was correlated with the estimated glomerular filtration rate ( r = 0.20, P = 0.001), left ventricular ejection fraction ( r = 0.13, P < 0.001), B‐type natriuretic peptide ( r = −0.28, P < 0.001), and lactate ( r = −0.15, P < 0.001). Kaplan–Meier curve of PaCO 2 tertiles and multivariate Cox regression analysis showed that the lowest PaCO 2 tertile was associated with increased risk of in‐hosp...
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