The inhibitory regulators, known as immune checkpoints, prevent overreaction of the immune system, avoid normal tissue damage, and maintain immune homeostasis during the antimicrobial or antiviral immune response. Unfortunately, cancer cells can mimic the ligands of immune checkpoints to evade immune surveillance. Application of immune checkpoint blockade can help dampen the ligands expressed on cancer cells, reverse the exhaustion status of effector T cells, and reinvigorate the antitumor function. Here, we briefly introduce the structure, expression, signaling pathway, and targeted drugs of several inhibitory immune checkpoints (PD-1/PD-L1, CTLA-4, TIM-3, LAG-3, VISTA, and IDO1). And we summarize the application of immune checkpoint inhibitors in tumors, such as single agent and combination therapy and adverse reactions. At the same time, we further discussed the correlation between immune checkpoints and microorganisms and the role of immune checkpoints in microbial-infection diseases. This review focused on the current knowledge about the role of the immune checkpoints will help in applying immune checkpoints for clinical therapy of cancer and other diseases.

The invasion and metastasis of malignant tumors are major causes of death. The most common metastases of cancer are lymphatic metastasis and hematogenous metastasis. Hematogenous metastasis often leads to rapid tumor dissemination. The mechanism of hematogenous metastasis of malignant tumors is very complex. Some experts have found that platelets play an important role in promoting tumor hematogenous metastasis. Platelets may be involved in many processes, such as promoting tumor cell survival, helping tumor cells escape immune surveillance, helping tumors attach to endothelial cells and penetrating capillaries for distant metastasis. However, recent studies have shown that platelets can also inhibit tumor metastasis. At present, the function of platelets in tumor progression has been widely studied, and they not only promote tumor cell metastasis, but also have an inhibitory effect. Therefore, in-depth and summary research of the molecular mechanism of platelets in tumor cell metastasis is of great significance for the screening and treatment of cancer patients. The following is a brief review of the role of platelets in the process of malignant tumor metastasis.

Breast cancer is one of the most common malignant tumors in women. It is a heterogeneous disease related to genetic and environmental factors. Presently, the treatment of breast cancer still faces challenges due to recurrence and metastasis. The emergence of single-cell RNA sequencing (scRNA-seq) technology has brought new strategies to deeply understand the biological behaviors of breast cancer. By analyzing cell phenotypes and transcriptome differences at the single-cell level, scRNA-seq reveals the heterogeneity, dynamic growth and differentiation process of cells. This review summarizes the application of scRNA-seq technology in breast cancer research, such as in studies on cell heterogeneity, cancer cell metastasis, drug resistance, and prognosis. scRNA-seq technology is of great significance to deeply analyze the mechanism of breast cancer occurrence and development, identify new therapeutic targets and develop new therapeutic approaches for breast cancer.

Copper is an essential cofactor for all organisms. However, it can become toxic if its concentration rises above a specific level. This level is controlled by evolutionary conserved homeostatic mechanisms. Recently, a new type of cell death called cuproptosis has been found. The process represents a copper-dependent, regulated form of cell death that is distinct from all known death mechanisms and relies on mitochondrial respiration. The mechanism of cuproptosis involves the direct binding of copper to lipidated parts in the tricarboxylic acid (TCA) cycle. This results in the abnormal aggregation of lipoylated proteins and the destabilization of iron-sulfur cluster (Fe-S) proteins. These events induce proteotoxic stress, ultimately leading to cell death. Copper-induced cell death is controlled by proteolipid acylation, which is mediated by the mitochondrial iron-sulfur protein FDX1. Copper overload also inhibits the biosynthesis of iron-sulfur (Fe-S) clusters and impairs the activity of Fe-S enzymes. As a result, mitochondrial function is disrupted. Both copper-induced cell death and impaired copper homeostasis arise from the same mechanistic basis. The expression of copper import gene SLC31A1 (CTR1) and export genes ATP7A and ATP7B significantly influences cuproptosis. The tumor suppressor p53 may participate in this process by modulating glycolysis and mitochondrial metabolism. In contrast, glutathione (GSH) reduces copper ion cytotoxicity by binding copper to form a complex. The growth and spread of tumor cells is more dependent on copper than that of normal cells.The copper ionophore elesclomol (ES) kills cancer cells by transporting copper ions into them. This ES-Cu complex not only inhibits cancer cell proliferation but also activates an immune response. Moreover, when ES is combined with αPD-L1, it might increase the effectiveness of cancer treatment. This gives a new idea for treating cancer.

The contribution of oncogenes to tumor-associated RNA splicing and the relevant molecular mechanisms therein require further elaboration. Here, we show that oncogenic Aurora kinase A (AURKA) promotes breast cancer-related RNA aberrant splicing in a context-dependent manner. AURKA regulated pan-breast cancer-associated RNA splicing events including GOLGA4, RBM4 and UBQLN1. Aberrant splicing of GOLGA4 and RBM4 was closely related to breast cancer development. Mechanistically, AURKA interacted with the splicing factor YBX1 and promoted AURKA-YBX1 complex-mediated GOLGA4 exon inclusion. AURKA binding to the splicing factor hnRNPK promoted AURKA-hnRNPK complex-mediated RBM4 exon skipping. Analysis of clinical data identified an association between the AURKA-YBX1/hnRNPK complex and poor prognosis in breast cancer. Blocking AURKA nuclear translocation with small molecule drugs partially reversed the oncogenic splicing of RBM4 and GOLGA4 in breast cancer cells. In summary, oncogenic AURKA executes its function on modulating breast cancer-related RNA splicing, and nuclear AURKA is distinguished as a hopeful target in the case of treating breast cancer.

Increasing evidence has demonstrated the crosstalk between DNA epigenetic alterations and aberrant expression of long non-coding RNAs (lncRNAs) during carcinogenesis. However, epigenetically dysregulated lncRNAs and their functional and clinical roles in Head and Neck Squamous Cell Carcinoma (HNSCC) are still not explored. In this study, we performed an integrative analysis of DNA methylation data and transcriptome data and identified a DNA methylation-dysregulated four-lncRNA signature (DNAMeFourLncSig) from 596 DNA methylation-dysregulated lncRNAs using a machine-learning-based feature selection method, which classified the patients of the discovery cohort into two risk groups with significantly different survival including overall survival, disease-specific survival, and progression-free survival. Then the DNAMeFourLncSig was implemented to another two HNSCC patient cohorts and showed similar prognostic values in both. Results from multivariable Cox regression analysis revealed that the DNAMeFourLncSig might be an independent prognostic factor. Furthermore, the DNAMeFourLncSig was substantially correlated with the complete response rate of chemotherapy and may predict chemotherapy response. Functional in silico analysis found that DNAMeFourLncSig-related mRNAs were mainly enriched in cell differentiation, tissue development and immune-related pathways. Overall, our study will improve our understanding of underlying transcriptional and epigenetic mechanisms in HNSCC carcinogenesis and provided a new potential biomarker for the prognosis of patients with HNSCC.