Programmed cell death (PCD) is a basic process of life that is closely related to the growth, development, aging and disease of organisms and is one of the hotspots of life science research today. PCD is a kind of genetic control, autonomous and orderly important cell death that involves the activation, expression, and regulation of a series of genes. In recent years, with the deepening of research in this field, new mechanisms of multiple PCD pathways have been revealed. This article reviews and summarizes the multiple PCD pathways that have been discovered, analyses and compares the morphological characteristics and biomarkers of different types of PCD, and briefly discusses the role of various types of PCD in the diagnosis and treatment of different diseases, especially malignant tumors.

Glioblastoma is the most lethal intracranial primary malignancy by no optimal treatment option. Cancer immunotherapy has achieved remarkable survival benefits against various advanced tumors, such as melanoma and non-small-cell lung cancer, thus triggering great interest as a new therapeutic strategy for glioblastoma. Moreover, the central nervous system has been rediscovered recently as a region for active immunosurveillance. There are vibrant investigations for successful glioblastoma immunotherapy despite the fact that initial clinical trial results are somewhat disappointing with unique challenges including T-cell dysfunction in the patients. This review will explore the potential of current immunotherapy modalities for glioblastoma treatment, especially focusing on major immune checkpoint inhibitors and the future strategies with novel targets and combo therapies. Immune-related adverse events and clinical challenges in glioblastoma immunotherapy are also summarized. Glioblastoma provides persistent difficulties for immunotherapy with a complex state of patients’ immune dysfunction and a variety of constraints in drug delivery to the central nervous system. However, rational design of combinational regimens and new focuses on myeloid cells and novel targets to circumvent current limitations hold promise to advent truly viable immunotherapy for glioblastoma.

Dysregulation or abnormality of the programmed cell death (PCD) pathway is closely related to the occurrence and development of many tumors, including acute myeloid leukemia (AML). Studying the abnormal characteristics of PCD pathway-related molecular markers can provide a basis for prognosis prediction and targeted drug design in AML patients. A total of 1394 genes representing 13 different PCD pathways were examined in AML patients and healthy donors. The upregulated genes were analyzed for their ability to predict overall survival (OS) individually, and these prognostic genes were subsequently combined to construct a PCD-related prognostic signature via an integrated approach consisting of 101 models based on ten machine learning algorithms. RNA transcriptome and clinical data from multiple AML cohorts (TCGA-AML, GSE106291, GSE146173 and Beat AML) were obtained to develop and validate the AML prognostic model. A total of 214 upregulated PCD-related genes were identified in AML patients, 39 of which were proven to be prognostic genes in the training cohort. On the basis of the average C-index and number of model genes identified from the machine learning combinations, a PCD index was developed and validated for predicting AML OS. A prognostic nomogram was then generated and validated on the basis of the PCD index, age and ELN risk stratification in the Beat AML cohort and the GSE146173 cohort, revealing satisfactory predictive power (AUC values ≥ 0.7). With different mutation patterns, a higher PCD index was associated with a worse OS. The PCD index was significantly related to higher scores for immunosuppressive cells and mature leukemia cell subtypes. As the gene most closely related to the PCD index, the expression of SMAD3 was further validated in vitro. AML cells harboring KMT2A rearrangements were more sensitive to the SMAD3 inhibitor SIS3, and the expression of the autophagy-related molecular marker LC3 was increased in KMT2A-rearranged cell lines after SIS3 monotherapy and combined treatment. The PCD index and SMAD3 gene expression levels have potential prognostic value and can be used in targeted therapy for AML, and these findings can lead to the development of effective strategies for the combined treatment of high-risk AML patients.

Cancer immunotherapy has attracted great attention as a potential therapeutic approach for advanced malignancies due to its promising survival benefits. Comprehension of intricate interactions between the tumor microenvironment (TME) and immune checkpoint inhibitors (ICIs) is crucial for optimizing and improving immunotherapies. Currently, several experimental strategies are available to monitor this complexity but most of them fail to facilitate real-time monitoring of the immune response such as cellular phagocytosis and cytolysis. Consequently, the application of intravital imaging has been extensively studied in the domain of cancer immunotherapy. Intravital imaging has been proven to be a powerful real-time imaging modality that provides insights into intratumoral immune responses, cellular metabolic signatures, tumor vasculature, and cellular functions. This review aims to provide a comprehensive overview of the latest research on intravital imaging in cancer immunotherapy, especially addressing how intravital imaging sheds light on essential features of tumor immunity, immune infiltrations, tumor angiogenesis, and aids in the clarification of underlying immunotherapeutic mechanisms. Moreover, a variety of labeling tools, imaging windows and models for real-time visualizations of TME are also summarized. We will also investigate the full potential of using intravital imaging to circumvent the limitations of currently available imaging modalities, which hold promise to advent efficient immunotherapy for cancer patients. Graphical abstract

Background: Ankyrin repeat domain 53 (ANKRD53) plays an important role in maintaining chromosome integrity and stability, and chromosome instability is associated with cancer. Through integrative analysis, this study investigates the potential value of ANKRD53 in stomach adenocarcinoma (STAD). Methods: RNA-seq and scRNA-seq data were used for integrative analysis based on online databases. Expression of ANKRD53 was confirmed by RT-PCR after bioinformatic analysis. Kaplan–Meier and Cox regression analyses were performed to evaluate the prognostic value of ANKRD53 in STAD. Gene set enrichment analysis (GSEA) was performed to evaluate ANKRD53-related signaling pathways. In addition, the interaction of ANKRD53 with immunity was also investigated. Results: RT-PCR in STAD cell lines confirmed that ANKRD53 was downregulated in STAD samples compared to normal samples in the online databases. As an independent predictive biomarker, ANKRD53 was combined with other clinicopathological parameters to create a prognostic nomogram. Using GSEA, ANKRD53 was found to be involved in five pathways, including the TGF-β signaling pathway. Further investigation revealed that ANKRD53 was associated with immune checkpoint molecules, immunological pathways, and immunotherapy, in addition to MSI, TMB and neoantigens. In addition, scRNA-seq data revealed that ANKRD53 is mainly expressed in CD8⁺ T and dendritic cells. Conclusions: ANKRD53 is an important biomarker for STAD that deserves further attention.