Background: Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) promote tumor immune tolerance and cause tumor immunotherapy failure. In this study, we found that high PMN-MDSCs infiltration, overexpressed fatty acid transporter protein 2 (FATP2) and underexpressed receptor-interacting protein kinase 3 (RIPK3) existed in the mouse and human bladder cancer tissues. However, the related mechanisms remain largely unknown.
Methods And Results: Both FATP2 and RIPK3 expressions were associated with clinical stage. FATP2 knockout or up-regulating RIPK3 reduced the synthesis of prostaglandin E2 (PGE2) in PMN-MDSCs, attenuated the suppressive activity of PMN-MDSCs on CD8 T cells functions and inhibited the tumor growth. There was a PGE2-mediated feedback loop between FATP2 and RIPK3 pathways, which markedly promoted the immunosuppressive activity of PMN-MDSCs. Combination therapy with inhibition of FATP2 and activation of RIPK3 can effectively inhibit tumor growth.
Conclusions: This study demonstrated that a feedback loop between FATP2 and RIPK3 pathways in PMN-MDSCs significantly promoted the synthesis of PGE2, which severely impaired the CD8 T cell functions. This study may provide new ideas for immunotherapy of human bladder cancer.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s11033-022-07924-x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Enhancing electric vehicle battery lifespan: integrating active balancing and machine learning for precise RUL estimation.
Sci Rep
January 2025
Electronics and Communication Engineering Dept. Faculty of Engineering, Horus University, New Damietta, Egypt.
Electric vehicles (EVs) rely heavily on lithium-ion battery packs as essential energy storage components. However, inconsistencies in cell characteristics and operating conditions can lead to imbalanced state of charge (SOC) levels, resulting in reduced capacity and accelerated degradation. This study presents an active cell balancing method optimized for both charging and discharging scenarios, aiming to equalize SOC across cells and improve overall pack performance.
View Article and Find Full Text PDFSpatial and single-cell transcriptomics reveal cellular heterogeneity and a novel cancer-promoting Treg cell subset in human clear-cell renal cell carcinoma.
J Immunother Cancer
January 2025
National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, Shaanxi, China
Background: Clear cell renal cell carcinoma (ccRCC) is the most common histologic type of RCC. However, the spatial and functional heterogeneity of immunosuppressive cells and the mechanisms by which their interactions promote immunosuppression in the ccRCC have not been thoroughly investigated.
Methods: To further investigate the cellular and regional heterogeneity of ccRCC, we analyzed single-cell and spatial transcriptome RNA sequencing data from four patients, which were obtained from samples from multiple regions, including the tumor core, tumor-normal interface, and distal normal tissue.
Adaptive average arterial pressure control by multi-agent on-policy reinforcement learning.
Sci Rep
January 2025
Multidisciplinary Center for Infrastructure Engineering, Shenyang University of Technology, Shenyang, 110870, China.
The current research introduces a model-free ultra-local model (MFULM) controller that utilizes the multi-agent on-policy reinforcement learning (MAOPRL) technique for remotely regulating blood pressure through precise drug dosing in a closed-loop system. Within the closed-loop system, there exists a MFULM controller, an observer, and an intelligent MAOPRL algorithm. Initially, a flexible MFULM controller is created to make adjustments to blood pressure and medication dosages.
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
Amsterdam UMC, Amsterdam, Netherlands.
Background: The TMEM106B protein is critical for proper functioning of the endolysomal system, which is utilised by all cells to traffic and degrade molecular cargo. Genome-wide association studies identified a haplotype in the TMEM106B gene that is associated with increased risk for Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and frontotemporal lobar degeneration with TAR DNA binding protein inclusions (FTLD-TDP). However, the causal variant that drives the association has thus far remained elusive.
View Article and Find Full Text PDFDigital Feedback Loop in Paraxial Fluids of Light: A Gate to New Phenomena in Analog Physical Simulations.
Phys Rev Lett
December 2024
Departamento de Física e Astronomia, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre s/n, 4169-007 Porto, Portugal and INESC TEC, Centre of Applied Photonics, Rua do Campo Alegre 687, 4169-007 Porto, Portugal.
Easily accessible through tabletop experiments, paraxial fluids of light are emerging as promising platforms for the simulation and exploration of quantumlike phenomena. In particular, the analogy builds on a formal equivalence between the governing model for a Bose-Einstein condensate under the mean-field approximation and the model of laser propagation inside nonlinear optical media under the paraxial approximation. Yet, the fact that the role of time is played by the propagation distance in the analog system imposes strong bounds on the range of accessible phenomena due to the limited length of the nonlinear medium.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!