Ferroptosis is a newly described type of programmed cell death and intensively related to both maintaining homeostasis and the development of diseases, especially cancers. Inducing ferroptosis leads to mitochondrial dysfunction and toxic lipid peroxidation in cells, which plays a pivotal role in suppressing cancer growth and progression. Here, we reviewed the existing studies about the molecular mechanisms of ferroptosis involved in different antitumor treatments, such as chemotherapy, targeted therapy, radiotherapy, and immunotherapy. We focused in particular on the distinct combinatorial therapeutic effects such as the synergistic sensitization effect and the drug-resistance reversal achieved when using ferroptosis inducers with conventional cancer therapy. Finally, we discussed the challenges and opportunities in clinical applications of ferroptosis. The application of nanotechnolgy and other novel technologies may provide a new direction in ferroptosis-driven cancer therapies.

Glioblastoma is considered to be the most malignant disease of the central nervous system, and it is often associated with poor survival. The immune microenvironment plays a key role in the development and treatment of glioblastoma. Among the different types of immune cells, tumor-associated microglia/macrophages (TAM/Ms) and CD8-positive (CD8+) T cells are the predominant immune cells, as well as the most active ones. Current studies have suggested that interaction between TAM/Ms and CD8+ T cells have numerous potential targets that will allow them to overcome malignancy in glioblastoma. In this review, we summarize the mechanism and function of TAM/Ms and CD8+ T cells involved in glioblastoma, as well as update on the relationship and crosstalk between these two cell types, to determine whether this association alters the immune status during glioblastoma development and affects optimal treatment. We focus on the molecular factors that are crucial to this interaction, and the role that this crosstalk plays in the biological processes underlying glioblastoma treatment, particularly with regard to immune therapy. We also discuss novel therapeutic targets that can aid in resolving reticular connections between TAM/Ms and CD8+ T cells, including depletion and reprogramming TAM/Ms and novel TAM/Ms-CD8+ T cell cofactors with potential translational usage. In addition, we highlight the challenges and discuss future perspectives of this crosstalk between TAM/Ms and CD8+ T cells.

Accumulating evidence indicates that aberrant regulation of metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1), a long noncoding RNA, plays a vital role in tumorigenesis. However, its association with breast cancer has not been systematically evaluated. In the current study, a meta-analysis was conducted to clarify the association between MALAT-1 and the prognosis and clinicopathological features of breast cancer. Relevant literature published in several databases was searched. Hazard ratio (HR) and odds ratio (OR) with 95% confidence interval (CI) were calculated to evaluate the effect of MALAT-1 expression on the survival outcomes and clinicopathological features of breast cancer. A total of 12 studies involving 4,106 patients were identified. Pooled HR demonstrated that elevated MALAT-1 expression significantly predicted unfavorable overall survival (HR=2.06, 95% CI: 1.66–2.56, P<0.0001) in patients with breast cancer. Subgroup analysis stratified by cancer type, sample size, and method of variance analysis also showed statistically significant associations. Additionally, the HR of patients with upregulated MALAT-1 expression concerning disease-free survival, recurrence-free survival, and disease-specific survival was 1.91 (95% CI: 1.53–2.39, P<0.0001). Further, elevated MALAT-1 expression was positively correlated with the progesterone receptor status (OR=1.47, 95% CI: 1.18–1.82). Thus, MALAT-1 is a promising biomarker for predicting survival outcomes in patients with breast cancer.

Background: Turning the “cold” tumor immune microenvironment into “hot” is a critical issue in cancer treatment today. Hormone receptor-rich breast cancer (HR+ BC) was previously considered immunologically quiescent. Objective: This study aims to explore the immunomodulatory effects of endocrine therapy on HR+ BCs. Methods: The infiltrations and alterations of the tumor immune microenvironment in HR+ BCs before, after 10-14 days, and after three months of neoadjuvant endocrine therapy were computationally analyzed according to MCP-counter, CIBERSORT, xCell algorithms, and gene-set enrichment analysis (GSEA). The primary microarray data were obtained from three HR+ BC gene expression datasets (GSE20181, GSE55374, and GSE59515). Single-sample GSEA of hallmark and immune response gene sets was performed to evaluate the correlation between suspected treatment response and activated immune pathways in tumors. Results: Both immune and stromal cells were specifically recruited into the HR+ BCs who responded to the neoadjuvant endocrine therapy by letrozole. Besides the enhanced infiltrations of immunosurveillance-related cells such as CD8+ T cells, dendritic cells, and the activation of immune response-related signals, the immunosuppressive M2-like macrophages, as well as the expression of immune checkpoint genes like PDCD1, SIRPA, and some HLA genes, were also stimulated in responders. We identified four pretreatment indicators (the intrinsic luminal subtype, the estrogen response early/late pathway, and the epithelial-mesenchymal transition pathway) as potential predictors of both clinical response and the activation of the tumor immune microenvironment post letrozole. Conclusions: Neoadjuvant endocrine therapy showed a promising way to convert the immunologically “cold” HR+ BCs into “hot” tumors. This study provides new insights into the application of immunotherapy for HR+ BCs especially those who respond to endocrine therapy.