【摘 要】
：
Metabolic regulation has been proven to play a critical role in T cell antitumor immunity.However,cholesterol metabolism as a key component of this regulation r
【机 构】
：
Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan 528308,
论文部分内容阅读
Metabolic regulation has been proven to play a critical role in T cell antitumor immunity.However,cholesterol metabolism as a key component of this regulation remains largely unexplored.Herein,we found that the low-density lipoprotein receptor (LDLR),which has been previously identified as a transporter for cholesterol,plays a pivotal role in regulating CD8+ T cell antitumor activity.Besides the involvement of cholesterol uptake which is mediated by LDLR in T cell priming and clonal expansion,we also found a non-canonical function of LDLR in CD8+ T cells: LDLR interacts with the T-cell receptor (TCR) complex and regulates TCR recycling and signaling,thus facilitating the effector function of cytotoxic T-lymphocytes (CTLs).Furthermore,we found that the tumor microenvironment (TME) downregulates CD8+ T cell LDLR level and TCR signaling via tumor cell-derived proprotein convertase subtilisin/kexin type 9 (PCSK9) which binds to LDLR and prevents the recycling of LDLR and TCR to the plasma membrane thus inhibits the effector function of CTLs.Moreover,genetic deletion or pharmacological inhibition of PCSK9 in tumor cells can enhance the antitumor activity of CD8+ T cells by alleviating the suppressive effect on CD8+ T cells and consequently inhibit tumor progression.While previously established as a hypercholesterolemia target,this study highlights PCSK9/LDLR as a potential target for cancer immunotherapy as well.
其他文献
Growth and immunity are opposing processes that compete for cellular resources,and proper resource allocation is crucial for plant survival.BSK1 plays a key rol
N6-methyladenosine (m6A),a ubiquitous internal modification of eukaryotic mRNAs,plays a vital role in almost every aspect of mRNA metabolism.However,there is li
The sessile nature of plants has promoted the evolution of a wide range of mechanisms that enable plants to adapt to the changing environment.In particular, the
Higher plants evolved multiple innate immune systems to combat pathogens present in their living environment.However, activation of the complex immune responses
For decades, practical limitations and cost have created a bias in plant genetic studies toward species that tolerate self pollination.An important work by Chen
The complexity of the epigenome landscape and transcriptional regulation is significantly increased during plant polyploidization,which drives genome evolution
Dear Editor,rnUrine passes through the entire kidney and urinary tract system starting from the glomerulus and ending to the urethra.Cells in the kidney and uri
High fidelity two-qubit gates are fundamental for scaling up the superconducting qubit number.We use two qubits coupled via a frequency-tunable coupler which ca
Coherent photon source is an important element that has been widely used in spectroscopy,imaging,detection,and teleportation in quantum optics.However,it is sti