NLRC5 overexpression in ovarian tumors remodels the tumor microenvironment and increases T-cell reactivity toward autologous tumor-associated antigens

IntroductionEpithelial ovarian cancer (OC) stands as one of the deadliest gynecologic malignancies, urgently necessitating novel therapeutic strategies. Approximately 60% of ovarian tumors exhibit reduced expression of major histocompatibility complex class I (MHC I), intensifying immune evasion mechanisms and rendering immunotherapies ineffective. NOD-like receptor CARD domain containing 5 (NLRC5) transcriptionally regulates MHC I genes and many antigen presentation machinery components. We therefore explored the therapeutic potential of NLRC5 in OC.MethodsWe generated OC cells overexpressing NLRC5 to rescue MHC I expression and antigen presentation and then assessed their capability to respond to PD-L1 blockade and an infected cell vaccine.ResultsAnalysis of microarray datasets revealed a correlation between elevated NLRC5 expression and extended survival in OC patients; however, NLRC5 was scarcely detected in the OC tumor microenvironment. OC cells overexpressing NLRC5 exhibited slower tumor growth and resulted in higher recruitment of leukocytes in the TME with lower CD4/CD8 T-cell ratios and increased activation of T cells. Immune cells from peripheral blood, spleen, and ascites from these mice displayed heightened activation and interferon-gamma production when exposed to autologous tumor-associated antigens. Finally, as a proof of concept, NLRC5 overexpression within an infected cell vaccine platform enhanced responses and prolonged survival in comparison with control groups when challenged with parental tumors.DiscussionThese findings provide a compelling rationale for utilizing NLRC5 overexpression in “cold” tumor models to enhance tumor susceptibility to T-cell recognition and elimination by boosting the presentation of endogenous tumor antigens. This approach holds promise for improving antitumoral immune responses in OC

Developing a safe water atlas for sustainable drinking water supply in Sonargaon Upazila, Bangladesh

Bangladesh has been relying heavily on groundwater for drinking and irrigation purposes since the 1960s. The access to safe drinking water has always been a challenge for Bangladesh due to the geogenic contamination in shallow aquifers. The objective of this study was to identify the depth for extracting safe water and to develop a safe water atlas for different unions of Sonargaon Upazila to ensure a year-round safe water supply. The concentrations of Arsenic, Iron and Manganese in groundwater were measured from 63 random water samples and compared with WHO and national drinking water quality standards. A lithological profile of the study area was developed to validate the indigenous knowledge of targeting safe depth based on sediment color. To address the challenges of groundwater depletion and contamination, the study identified and developed the technique of preparing safe water atlas for a specific region in Bangladesh, serving as a decision-making tool for households. The atlas identifies depths at which tube-wells can be installed to obtain uncontaminated groundwater, helping people make informed choices and avoid potential health risks. Additionally, the safe water atlas can support the development of safe drinking water distribution plans and assist local drillers and residents in decision-making processes.We are grateful to the local drillers of Sonargaon Upazila who helped us with the data collection. We would also like to acknowledge the contribution of anonymous reviewers in editing the paper.Peer reviewe