CKLF instigates a "cold" microenvironment to promote MYCN-mediated tumor aggressiveness.

Solid tumors, especially those with aberrant MYCN activation, often harbor an immunosuppressive microenvironment to fuel malignant growth and trigger treatment resistance. Despite this knowledge, there are no effective strategies to tackle this problem. We found that chemokine-like factor (CKLF) is highly expressed by various solid tumor cells and transcriptionally up-regulated by MYCN. Using the MYCN-driven high-risk neuroblastoma as a model system, we demonstrated that as early as the premalignant stage, tumor cells secrete CKLF to attract CCR4-expressing CD4+ cells, inducing immunosuppression and tumor aggression. Genetic depletion of CD4+ T regulatory cells abolishes the immunorestrictive and protumorigenic effects of CKLF. Our work supports that disrupting CKLF-mediated cross-talk between tumor and CD4+ suppressor cells represents a promising immunotherapeutic approach to battling MYCN-driven tumors.

Effectiveness of a novel bubble CPAP system for neonatal respiratory support at a referral hospital in the Philippines.

Aim: To examine the impact of introducing and implementing the Vayu bubble continuous positive airway pressure (bCPAP) system on neonatal survival and neonatal respiratory outcomes in a neonatal intensive care unit (NICU) in the Philippines. Methods: We compared clinical outcomes of 1,024 neonates before to 979 neonates after introduction of Vayu bCPAP systems into a NICU. The primary outcome was survival to discharge. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were calculated. Analyses were undertaken separately for the entire NICU population and for neonates who received any form of respiratory support. Results: The introduction of the Vayu bCPAP system was associated with (1) significant reductions in intubation (aOR: 0.75; 95% CI: 0.58-0.96) and in the use of nasal intermittent positive-pressure ventilation (NIPPV) (aOR: 0.69; 95% CI: 0.50-0.96) among the entire NICU population and (2) a significant increase in survival to discharge (aOR: 1.53; 95% CI: 1.09-2.17) and significant reductions in intubation (aOR: 0.52; 95% CI: 0.38-0.71), surfactant administration (aOR: 0.60; 95% CI: 0.40-0.89), NIPPV use (aOR: 0.52; 95% CI: 0.36-0.76), and a composite neonatal adverse outcome (aOR: 0.60; 95% CI: 0.42-0.84) among neonates who received any form of respiratory support. Conclusion: The use of the Vayu bCPAP system in a NICU in the Philippines resulted in significant improvement in neonatal respiratory outcomes.

Tipping the Scales With Zebrafish to Understand Adaptive Tumor Immunity.

The future of improved immunotherapy against cancer depends on an in-depth understanding of the dynamic interactions between the immune system and tumors. Over the past two decades, the zebrafish has served as a valuable model system to provide fresh insights into both the development of the immune system and the etiologies of many different cancers. This well-established foundation of knowledge combined with the imaging and genetic capacities of the zebrafish provides a new frontier in cancer immunology research. In this review, we provide an overview of the development of the zebrafish immune system along with a side-by-side comparison of its human counterpart. We then introduce components of the adaptive immune system with a focus on their roles in the tumor microenvironment (TME) of teleosts. In addition, we summarize zebrafish models developed for the study of cancer and adaptive immunity along with other available tools and technology afforded by this experimental system. Finally, we discuss some recent research conducted using the zebrafish to investigate adaptive immune cell-tumor interactions. Without a doubt, the zebrafish will arise as one of the driving forces to help expand the knowledge of tumor immunity and facilitate the development of improved anti-cancer immunotherapy in the foreseeable future.