Androgen receptor–positive prostate cancer (PCa) and estrogen receptor–positive luminal breast cancer (BCa) are generally less responsive to immunotherapy compared with certain tumor types such as melanoma. However, the underlying mechanisms are not fully elucidated. In this study, we found that FOXA1 overexpression inversely correlated with interferon (IFN) signature and antigen presentation gene expression in PCa and BCa patients. FOXA1 bound the STAT2 DNA-binding domain and suppressed STAT2 DNA-binding activity, IFN signaling gene expression, and cancer immune response independently of the transactivation activity of FOXA1 and its mutations detected in PCa and BCa. Increased FOXA1 expression promoted cancer immuno- and chemotherapy resistance in mice and PCa and BCa patients. These findings were also validated in bladder cancer expressing high levels of FOXA1. FOXA1 overexpression could be a prognostic factor to predict therapy resistance and a viable target to sensitize luminal PCa, BCa, and bladder cancer to immuno- and chemotherapy.

Objectives: Obesity has become a common health concern around the world. Maternal obesity could cause poor reproductive outcomes due to chronic ovarian inflammation and decreased oocyte quality. However, the strategies to improve the poor reproductive outcomes of obese females have not been fully studied. In this study, we aimed to explore the effects and underlying mechanisms of nicotinamide mononucleotide (NMN) on oocyte quality and reproductive performance of obese mice.Materials and Methods: The obese mouse model was established by feeding high‐fat diet which was confirmed by body weight record, fasting blood glucose test and oral glucose tolerance test. The expression of ovary development related genes and inflammation related genes, including Lhx8, Bmp4, Adgre1, Ccl2, TNF‐α, Gal‐3, Clec10a and IL‐10 in ovaries and the expression of Bax and Sod1 in oocytes were detected using quantitative reverse transcription PCR (RT‐qPCR). The adipose size of abdominal fat tissue was determined with haematoxylin and eosin (H&E) staining. Immunofluorescence staining was performed to measure the ROS level, spindle/chromosome structure, mitochondrial function, actin dynamics and DNA damage of oocytes.Results: The administration of NMN restored ovarian weight and reduced the adipose size of abdominal fat tissue and ovarian inflammation in high fat diet (HFD) mice. Furthermore, NMN treatment improved the oocytes quality partially by restoring the mitochondrial function and actin dynamics, reducing meiotic defects, DNA damage and ROS level and lipid droplet distribution of oocytes in HFD mice. On the long‐term effect, NMN restored offspring body weight of HFD mice.Conclusion: NMN could improve the oocyte quality of HFD‐induced obese mice.

Breast cancer (BC) is the most frequently diagnosed malignant tumor among women in the world. BC is the heterogeneous tumor with different subtypes including luminal A-like, luminal B-like (HER2-/HER2+), HER2 enriched, and triple-negative BC. The therapeutic strategies including surgery, chemotherapy, radiotherapy, targeted therapy, and endocrine therapy are well developed and commonly used in the treatment of BC. However, some adverse effects of these conventional treatments limited their wide application in clinical. Therefore, it is necessary to develop more safe and more efficient individualized treatment strategies of the BC. Nanomedicine, as the most promising strategy for controlled and targeted drug delivery, is widely used in multiple aspects of cancer therapy. Importantly, accumulative evidences show that nanomedicine has achieved good outcomes in the treatment of BC and a huge amount of BC patients benefited from the nanomedicine related treatments. In this review, we summarized and discussed the major problems occurred during the administration of conventional treatment strategies for BC and the potential roles of nanomedicine in promoting the treatment efficacy of BC by overcoming obstacles of current treatment of BC.

Myocardial infarction is a cardiovascular disease with high mortality. Human umbilical cord mesenchymal stem cells (hUC-MSCs) with strong self-renewal capacity and multipotency, provide the possibility of replacing injured cardiomyocytes. hUC-MSCs were cultured on polyacrylamide hydrogels with stiffnesses corresponding to Young's modulus of 13-16kPa and 62-68kPa which mimic the stiffnesses of healthy heart tissue and fibrotic myocardium. The expression of early myocardial markers Nkx2.5, GATA4, Mesp1 and the mature myocardial markers cTnT, cTnI, α-actin were detected by RT-PCR and Western Blot, which showed that soft matrix (13-16 kPa) tended to induce the differentiation of hUC-MSCs into myocardium, compared with stiff matrix (62-68 kPa). Piezos are mechanically sensitive non-selective cation channels. The expression of Piezo1 increased with the stiffness gradient of 1-10kPa, 13-16kPa, 35-38kPa and 62-68kPa on the 1st day, but Piezo2 expression was irregular. The expression of integrin β1 and calcium ions were also higher on stiff substrate than on soft substrate. hUC-MSCs tend to differentiate into myocardium on the matrix stiffness of 13-16 kPa. The relationship among matrix stiffness, Piezo1 and myocardial differentiation needs further validation.

Cancer immunotherapies, including immune checkpoint inhibition (ICI) and adoptive immune cells therapy, are promising therapeutic strategies. They reactivate the function of immune cells and induce immune responses to attack tumor cells. Although these novel therapies benefited a large amount of cancer patients, many cancer patients have shown fair responses even resistance to cancer immunotherapies, limiting their wide clinical application. Therefore, it is urgent to explore the underlying mechanisms of low response and resistance of cancer immunotherapy to enhance their treatment efficacy. The programmed cell death (PCD) including the ferroptosis, has been demonstrated to play essential roles in antitumor immunity and in regulating the immune response to ICIs. Ferroptosis, a phospholipid peroxidation-mediated, iron-dependent membrane damage, exhibite three critical hallmarks: the oxidation of phospholipids, the lack of lipid peroxide repair capability and the overloading of redox-active iron. Notably, ferroptosis was found to plays important roles in regulating tumor immunity and response to immunotherapy. Therefore, targeting ferroptosis alone or in combination with immunotherapy may provide novel options to promote their antitumor efficacy. However, the effect of ferroptosis on tumor immunity and immunotherapy is affected by the interaction of ferroptosis and cancer cells, immune cells, tumor microenvironment (TME) and others. In this review, we summarized and discussed the critical roles of ferroptosis in regulating antitumor immunity, TME and in the improvement of the therapeutic efficacy of immunotherapy in cancers.