NU-7427

Ovarian cancer (OV) is a malignant tumor that ranks first among gynecological cancers, thus posing a significant threat to women's health. Immunogenic cell death (ICD) can regulate cell death by activating the adaptive immune system. Here, we aimed to comprehensively characterize the features of ICD-associated genes in ovarian cancer, and to investigate their prognostic value and role in the response to immunotherapy. After analyzing datasets from The Cancer Genome Atlas, we utilized weighted gene coexpression network analysis to screen for hub genes strongly correlated with ICD genes in OV, which was subsequently validated with OV samples from the Gene Expression Omnibus (GEO) database. A prognostic risk model was then constructed after combining univariate, multivariate Cox regression and LASSO regression analysis to recognize nine ICD-associated molecules. Next, we stratified all OV patients into two subgroups according to the median value. The multivariate Cox regression analysis showed that the risk model could predict OV patient survival with good accuracy. The same results were also found in the validation set from GEO. We then compared the degree of immune cell infiltration in the tumor microenvironment between the two subgroups of OV patients, and revealed that the high-risk subtype had a higher degree of immune infiltration than the low-risk subtype. Additionally, in contrast to patients in the high-risk subgroup, those in the low-risk subgroup were more susceptible to chemotherapy. In conclusion, our research offers an independent and validated model concerning ICD-related molecules to estimate the prognosis, degree of immune infiltration, and chemotherapy susceptibility in patients with OV.

Triple-negative breast cancer (TNBC) presents a formidable challenge due to its poorest prognosis and limited array of treatment options available. Photodynamic therapy (PDT) has emerged as a potent therapeutic modality to generate intratumoral toxic reactive oxygen species (ROS) in combating refractory triple-negative breast cancer (TNBC). However, its therapeutic efficacy is compromised due to insufficient tumor accumulation and therapeutic resistance. Herein, an "all-in-one" tumor-therapeutic nanomedicine named HA@IR780@KU55933@BSA (HIKB) which integrated photosensitizer IR780 with ATM kinase inhibitor KU55933 was designed to facilitate drug delivery and target specific pathways involved in tumor PDT treatment resistance. Co-delivery of IR780 and KU55933 exacerbated intracellular ROS production, mitochondrial dysfunction and DNA damage to form a potent anti-TNBC therapeutic cyclical feedback loop and then induced pyroptosis and apoptosis of TNBC cells by activating the Caspase3/GSDME signaling pathway and regulating apoptosis-related protein expression, respectively. In vivo evaluations in the TNBC orthotopic xenograft mouse model demonstrated that the designed HIKB NPs could accumulate in tumor tissues and exert synergistic therapeutic effects. Altogether, this study described a self-assembling strategy for constructing an all-in-one nanomedicine that effectively integrates multiple therapeutic modalities to provide a comprehensive and systemic approach to tumor suppression.