Iron is an essential element for biological processes. Iron homeostasis is regulated through several mechanisms, from absorption by enterocytes to recycling by macrophages and storage in hepatocytes. Iron has dual properties, which may facilitate tumor growth or cell death. Cancer cells exhibit an increased dependence on iron compared with normal cells. Macrophages potentially deliver iron to cancer cells, resulting in tumor promotion. Mitochondria utilize cellular iron to synthesize cofactors, including heme and iron sulfur clusters. The latter is composed of essential enzymes involved in DNA synthesis and repair, oxidation-reduction reactions, and other cellular processes. However, highly increased iron concentrations result in cell death through membrane lipid peroxidation, termed ferroptosis. Ferroptosis, an emerging pathway for cancer treatment, is similar to pyroptosis, apoptosis and necroptosis. In the present review, previous studies on the physiology of iron metabolism and its role in cancer are summarized. Additionally, the significance of iron regulation, and the association between iron homeostasis and carcinogenic mechanisms are discussed. Contents 1. Introduction 2. Iron absorption 3. Iron distribution and excretion 4. Iron and various cancers 5. Mechanisms of iron-mediated proliferation of tumor cells 6. Ferroptosis: Iron-dependent cancer cell death 7. Conclusions

BackgroundIncreasing infiltration of CD8+ T cells within tumor tissue predicts a better prognosis and is essential for response to checkpoint blocking therapy. Furthermore, current clinical protocols use unfractioned T cell populations as the starting point for transduction of chimeric antigen receptors (CARs)-modified T cells, but the optimal T cell subtype of CAR-modified T cells remains unclear. Thus, accurately identifying a group of cytotoxic T lymphocytes with high antitumor efficacy is imperative. Inspired by the theory of yin and yang, we explored a subset of CD8+ T cell in cancer with the same phenotypic characteristics as highly activated inflammatory T cells in autoimmune diseases.MethodsCombination of single-cell RNA sequencing, general transcriptome sequencing data and multiparametric cytometric techniques allowed us to map CXCR6 expression on specific cell type and tissue. We applied Cxcr6−/− mice, immune checkpoint therapies and bone marrow chimeras to identify the function of CXCR6+CD8+ T cells. Transgenic Cxcr6−/− OT-I mice were employed to explore the functional role of CXCR6 in antigen-specific antitumor response.ResultsWe identified that CXCR6 was exclusively expressed on intratumoral CD8+ T cell. CXCR6+CD8+ T cells were more immunocompetent, and chimeras with specific deficiency on CD8+ T cells showed weaker antitumor activity. In addition, Cxcr6−/− mice could not respond to anti-PD-1 treatment effectively. High tumor expression of CXCR6 was not mainly caused by ligand-receptor chemotaxis of CXCL16/CXCR6 but induced by tumor tissue self. Induced CXCR6+CD8+ T cells possessed tumor antigen specificity and could enhance the effect of anti-PD-1 blockade to retard tumor progression.ConclusionsThis study may contribute to the rational design of combined immunotherapy. Alternatively, CXCR6 may be used as a biomarker for effective CD8+ T cell state before adoptive cell therapy, providing a basis for tumor immunotherapy.

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BackgroundBladder cancer (BC) is the most common cancer of the urinary bladder and upper tract, in which the clinical management is limited. AURKA (aurora kinase A) has been identified as an oncogene in cancer development; however, its potential role and underlying mechanisms in the progression of BC remain unknown.ResultsIn this study, we evaluated Aurora kinase A (AURKA) expression in patient samples by performing gene expression profiling, and found that AURKA expression levels were significantly higher in BC tissues than in normal tissues. Increased AURKA in BC was strongly associated with stage and grade. Moreover, BC patients with elevated AURKA achieved poor overall survival rates. The experiments in vitro comprehensively validated the critical role of AURKA in promoting BC cell proliferation using the methods of gene overexpression and gene silencing. Furthermore, we proved that AURKA inhibitor MLN8237 arrested BC cell growth and induced apoptosis.ConclusionsThese findings implicate AURKA acting as an effective biomarker for BC detection and prognosis, as well as therapeutic target.

Background: Without a doubt, nipple-sparing mastectomy affords a better cosmetic result than modified radical mastectomy. However, the surgical safety, radicality, complications, indications, and psychological benefits associated with this method are controversially discussed. Patients and Methods: We carried out a retrospective analysis of 35 patients (study group) who underwent nipple-sparing mastectomy between 2000 and 2008. Indications, incision selection, postoperative complications, recurrence, morbidity rate, and psychological status were recorded and assessed. Results: The survival outcome (5.7 vs. 6%; p = 0.35) and complication rate (5.7 vs. 19%; p = 0.062) of patients who underwent subcutaneous nipple-sparing mastectomy and immediate breast reconstruction with prosthesis were similar to those of patients who underwent modified radical mastectomy. Most patients in the study group were completely satisfied with the aesthetic results (immediately, p < 0.001; < 1 year, p < 0.001; > 1 year, p < 0.001), and no serious psychological disorders or stress were detected relative to patients with traditional mastectomy. Conclusion: Subcutaneous nipple-sparing mastectomy was beneficial and safe in this cohort of breast cancer patients. The approach is suitable for patients with isolated lesions located ≥ 2 cm from the nipple, as well as for patients with multiple lesions who are anxious about a good cosmetic appearance.