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10.1172/JCI127721 http://scihub22266oqcxt.onion/10.1172/JCI127721 31503548!6877338!31503548     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=31503548&cmd=llinks): Failed to open stream: HTTP request failed! 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Myeloid loss of Beclin 1 promotes PD-L1hi precursor B cell lymphoma development |pdf=|usr=}}{{31503548}} gab.com Text Myeloid loss of Beclin 1 promotes PD-L1hi precursor B cell lymphoma development JO: J Clin Invest http://www.kidney.de/pget.php?&tw=1&pmid=31503548 #FOAvip Beclin 1 (Becn1) is a key molecule in the autophagy pathway and has been implicated in cancer development. Due to the embryonic lethality of homozygous Becn1-deficient mice, the precise mechanisms and cell type-specific roles of Becn1 in regulating inflammation and cancer immunity remain elusive. Here, we report that myeloid-deficient Becn1 (Becn1DeltaM) mice developed neutrophilia, were hypersusceptible to LPS-induced septic shock, and had a high risk of developing spontaneous precursor B cell (pre-B cell) lymphoma with elevated expression of immunosuppressive molecules programmed death ligand 1 (PD-L1) and IL-10. Becn1 deficiency resulted in the stabilization of MEKK3 and aberrant p38 activation in neutrophils, and mediated neutrophil-B cell interaction through Cxcl9/Cxcr3 chemotaxis. Neutrophil-B cell interplay further led to the activation of IL-21/STAT3/IRF1 and CD40L/ERK signaling and PD-L1 expression; therefore, it suppressed CD8+ T cell function. Ablation of p38 in Becn1DeltaM mice prevented neutrophil inflammation and B cell tumorigenesis. Importantly, the low expression of Becn1 in human neutrophils was significantly correlated with the PD-L1 levels in pre-B acute lymphoblastic lymphoma (ALL) patients. Our findings have identified myeloid Becn1 as a key regulator of cancer immunity and therapeutic target for pre-B cell lymphomas. Twit Text FOAVip Myeloid loss of Beclin 1 promotes PD-L1hi precursor B cell lymphoma development ????J Clin Invest http://www.kidney.de/pget.php?&tw=1&pmid=31503548 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=31503548 #FOAvip English Wikipedia <ref>{{Cite pmid|31503548}}</ref> Myeloid loss of Beclin 1 promotes PD-L1hi precursor B cell lymphoma development #MMPMID31503548 Tan P; He L; Xing C; Mao J; Yu X; Zhu M; Diao L; Han L; Zhou Y; You MJ; Wang HY; Wang RF J Clin Invest 2019[Dec]; 129 (12): 5261-5277 PMID31503548show ga Beclin 1 (Becn1) is a key molecule in the autophagy pathway and has been implicated in cancer development. Due to the embryonic lethality of homozygous Becn1-deficient mice, the precise mechanisms and cell type-specific roles of Becn1 in regulating inflammation and cancer immunity remain elusive. Here, we report that myeloid-deficient Becn1 (Becn1DeltaM) mice developed neutrophilia, were hypersusceptible to LPS-induced septic shock, and had a high risk of developing spontaneous precursor B cell (pre-B cell) lymphoma with elevated expression of immunosuppressive molecules programmed death ligand 1 (PD-L1) and IL-10. Becn1 deficiency resulted in the stabilization of MEKK3 and aberrant p38 activation in neutrophils, and mediated neutrophil-B cell interaction through Cxcl9/Cxcr3 chemotaxis. Neutrophil-B cell interplay further led to the activation of IL-21/STAT3/IRF1 and CD40L/ERK signaling and PD-L1 expression; therefore, it suppressed CD8+ T cell function. Ablation of p38 in Becn1DeltaM mice prevented neutrophil inflammation and B cell tumorigenesis. Importantly, the low expression of Becn1 in human neutrophils was significantly correlated with the PD-L1 levels in pre-B acute lymphoblastic lymphoma (ALL) patients. Our findings have identified myeloid Becn1 as a key regulator of cancer immunity and therapeutic target for pre-B cell lymphomas. |Animals[MESH] |Autophagy[MESH] |B7-H1 Antigen/*metabolism[MESH] |Beclin-1/genetics/*metabolism[MESH] |CD8-Positive T-Lymphocytes/metabolism[MESH] |Chemotaxis[MESH] |Female[MESH] |Homozygote[MESH] |Humans[MESH] |Inflammation[MESH] |Lymphocyte Activation[MESH] |Lymphoma, B-Cell/*metabolism[MESH] |Lymphoma/metabolism[MESH] |MAP Kinase Kinase Kinase 3/metabolism[MESH] |Male[MESH] |Mice[MESH] |Neutrophils/metabolism[MESH] |Precursor Cells, B-Lymphoid/*metabolism[MESH] |Signal Transduction[MESH]Myeloid loss of Beclin 1 promotes PD-L1hi precursor B cell lymphoma de(epmc).pdf DeepDyve Pubget Overpricing