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Background Failure of glioblastoma (GBM) therapy is often ascribed to different types of glioblastoma stem-like cells (GSLCs) niche, in particularly, a hypoxic perivascular niche (HPVN) is involved in GBM progression. However, the responsible cells for HPVN remained unclear. Methods Immunostaining was performed to determine the cells that are responsible for HPVN. A hypoxic chamber and 3D microfluidic chips were designed to simulate HPVN based on the pathological features of GBM. The phenotype of GSLCs was evaluated by fluorescence scanning in real-time and proliferation and apoptotic assays. The expression of JAG1, DLL4 and Hes1 was determined by immunostaining, ELISA, western-blotting, and q-PCR. Their clinical progonostic significance in GBM HPVN and total tumor tissues were verified by clinical data and TCGA databases. Results Nestin +/CD31 + cells and pericytes constitute the major part of microvessels in HPVN and high ratio of nestin +/CD31 + cells rather than pericytes were responsible for poor prognosis of GBM. A more real HPVN was simulated by hypoxic coculture system in vitro, which was assembled by 3D microfluidic chips and hypoxic chamber. Nestin +/CD31 + cells in HPVN were derived from GSLCs transdifferentiation and could promote GSLCs chemoresistance by providing more JAG1 and DLL4 to induce down-stream Hes1 overexpression. Poor prognosis of GBM was correlated to Hes1 expression of tumor cells in GBM HPVN, and not correlated with total Hes1 expression in GBM tissues. Conclusion These results hightlighted the critical role of nestin +/CD31 + cells in HPVN that acts in GBM chemoresistance and revealed the distinctive prognostic value of these molecular markers in HPVN.

Rationale: Cancer immunotherapy has demonstrated significant antitumor activity in a variety of tumors; however, extensive infiltration of immunosuppressive tumor-associated macrophages (TAMs) in the glioblastoma (GBM) tumor microenvironment (TME) and the existence of the blood-brain barrier (BBB) might lead to failure of the checkpoint blockade therapy. Methods: Herein, we have developed a smart "Trojan horse" BBB-permeable nanocapsule termed "NAcp@CD47" to deliver anti-CD47 antibodies and stimulator of interferon genes (STING) agonists into GBM tissues in a stealth-like manner to reshaped the immune microenvironment by switching the phenotype of microglia and macrophages. Results: Both in vitro and in vivo studies demonstrate that NAcp@CD47 could effectively penetrate the BBB, increase the polarization of M1-phenotype TAMs, help reduce tumor immunosuppression, and inhibit the orthotopic GBM growth by phagocytosis of macrophages and microglia. Conclusions: Our findings indicate that the well-designed NAcp@CD47 not only enhances the phagocytosis of cancer cells but also efficiently enhance antitumor immunogenicity and reverses immune suppression to convert uninflamed "cold" tumors into "hot" tumors.

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Purpose This study assessed the prognostic value of red blood cell distribution width (RDW) and cancer antigen 125 (CA125) in predicting the prognosis of endometrial cancer (EC) patients. Patients and Methods In this study, we included 525 patients with EC between January 2013 and January 2019. Demographic and clinical indicators were collected, and the receiver operating characteristics curve (ROC) and cutoff values were calculated between the early and advanced stages of EC. Independent risk factors associated with EC prognosis were assessed using Cox regression analyses and the Kaplan–Meier method. Results Compared to women in the early stage of EC, women with advanced stage had significantly elevated RDW coefficient of variation (RDW-CV) and CA125 levels and lower mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) (both P < 0.05). Consequently, RDW-CV and CA125 were found to be independent risk factors for EC by using ROC curve and multivariate logistic regression analysis. The survival analysis curve was used to assess the diagnostic value of RDW-CV, CA125, and their combination in the prognosis of EC. The results showed that patients with high expression of RDW-CV and CA125 had worse overall survival than those with low expression. Moreover, multivariate Cox regression analysis indicated that RDW-CV+CA125=2 was an independent prognostic factor. Conclusion These findings suggest that CA125 combined with RDW-CV has a good prognostic value for EC. Thus, the RDW-CV+CA125 score is a promising prognostic marker for the clinical decision-making process regarding EC outcomes.