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Prosaposin hyperglycosylation: a novel tumor immune escape mechanism and implications for cancer immunotherapy

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3150-3152页

作者： Matthias Peipp Diana Dudziak Christian Kellner division of Antibody-Based Immunotherapy Department of Medicine IChristian-Albrechts University and University Hospital Schleswig-HolsteinKielGermany institute of immunology Jena University HospitalFriedrich-Schiller-UniversityJenaGermany Comprehensive Cancer Center Central Germany Jena/Leipzig JenaGermany division of Transfusion Medicine Cell Therapeutics and HaemostaseologyLMU University HospitalLMU MunichMunichGermany

In a recent article published in Science,Sharma et *** the essential role of saposins in cross-presentation of tumor membraneassociated antigens by dendritic cells(DC)to CD8^(+)T cells.1 However,antigen cross-presentation,which is fundamental in cancer cell elimination,is hindered in tumor DC by hyperglycosylation of the common saposin precursor prosaposin(pSAP)leading to impaired T cell tumor immunity-yet,the potential of recombinant pSAP to re-establish T cell responses may offer a novel way to counteract immune evasion in a therapeutic approach.

关键词： impaired immunity al.

c-myb is involved in CML progression and is a therapeutic target in the zebrafish CML model

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Animal Models and Experimental Medicine 2024年第2期7卷 136-144页

作者： Yin Ye Xiaojun Yang Feifei Li Wei Liu Wenqing Zhang Zhibin Huang division of cell Developmental and Integrative BiologySchool of MedicineSouth China University of TechnologyGuangzhouChina

Background:Despite the success of tyrosine kinase inhibitors in chronic myeloid leukemia(CML)therapy,CML still faces the challenges of drug resistance and progression to blast ***-five percent of patients have imatinib resistance and treatment difficulties due to heterogeneity after progression,but little is known about the mechanism.A key transcription factor in hematopoiesis,MYB,has been reported to increase abnormally in several types of aggressive blood disorders including ***:This study used a zebrafish model to explore the relationship between BCR/ABL1 and c-myb in CML progression.A CML zebrafish model was crossed with a c-myb hyperactivity transgenic ***:It was found that both exogenous BCR/ABL1 and c-myb could up-regulate the expression of neutrophil-related *** seriously,neutrophil accumulation was observed when BCR/ABL1 was combined with c-myb *** studies showed that c-myb may be one of the downstream targets of BCR/ABL1 and the effect of BCR/ABL1 on neutrophils was c-myb *** advantage of this inheritable in vivo model,it was shown that a combination of imatinib and flavopiridol,a cyclin-dependent kinase inhibitor targeting MYB,could more effectively alleviate the aggressive phenotype of the double transgene ***:In summary,this study suggests that c-myb acts downstream of BCR/ABL1 and is involved in CML progression and is therefore a risk factor and a valuable target for the treatment of CML *** model used in the study could be helpful in high-throughput drug screening in CML transformation.

关键词： chronic myeloid leukemia c-myb flavopiridol zebrafish model

Knockout of OsSPL10 confers enhanced glufosinate resistance in rice

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Plant Communications 2024年第2期5卷 7-10页

作者： Jin-Qiu Xia Qin-Yu Liang Da-Yu He Zheng-Yi Zhang Jie Wu Jing Zhang Ping-Xia Zhao Zi-Sheng Zhang Cheng-Bin Xiang division of Life Sciences and Medicine Division of Molecular&Cell BiophysicsHefei National Science Center for Physical Sciences at the MicroscaleUniversity of Science and Technology of ChinaThe Innovation Academy of Seed DesignChinese Academy of SciencesHefeiAnhui Province 230027China

Dear Editor,Rice(Oryza sativa L.)is one of the world’s major food crops,feeding more than half of the global *** reduce labor and production costs,direct seeding is becoming popular for rice cultivation,but weeds have become a serious problem(Jin et al.,2022).Chemical herbicides are one of the most effective ways to control ***,the development of herbicide-resistant rice has great significance for modern rice production.

关键词： crops population. weed

Unveiling the anticancer effect of traditional Chinese herbal medicine

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World Journal of Gastroenterology 2024年第30期30卷 3625-3627页

作者： Naoki Asano division of Carcinogenesis and Senescence Biology Tohoku University Graduate School of MedicineNatori 981-1293MiyagiJapan division of Cancer Stem cell Miyagi Cancer Center Research InstituteNatori 981-1293MiyagiJapan

In this issue of World Journal of Gastroenterology,Huang et al reported that Calculus bovis(CB),a traditional Chinese herbal medicine,impedes the growth of liver cancers in *** further in vitro studies,they showed that CB suppressed the M2 polarization of tumor-associated macrophages by suppressing the Wnt signaling pathway,which consequently inhibited the growth of liver *** the effects of traditional Chinese herbal medicine are often not scientifically proven,Huang et al successfully identified the molecular mechanism involved in the anticancer effect of CB,and it is anticipated that the molecular mechanisms involved in the effects of other traditional Chinese herbal medicines will be scientifically elucidated,as demonstrated in this article.

关键词： Calculus bovis Chinese herbal medicine Wnt Hepatocellular carcinoma Liver cancer Tumor-associated macrophages M2 polarization

Joint deletion of multifunctional MGF505-7R and H240R genes generates a safe and effective African swine fever virus attenuated live vaccine candidate

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Virologica Sinica 2024年第3期39卷 355-357页

作者： Changjiang Weng Li Huang Guangqiang Ye division of Fundamental immunology National African Swine Fever Para-reference LaboratoryState Key Laboratory for Animal Disease Control and PreventionHarbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150069China Heilongjiang Provincial Key Laboratory of Veterinary immunology Harbin 150069China

African swine fever(ASF)caused by the ASF virus(ASFV)is a highly contagious disease of pigs and wild ***,there are no safe,effective commercial vaccines *** genome of ASFV HLJ/18 contains more than 180 genes,including a few virulence-related *** these key virulence genes through individual deletion and subsequent pathogenicity testing in pigs is a laborious *** addition,some ASFV genes are indispensable for viral replication and cannot be *** the past 30 years,scientists have confirmed that certain ASFV genes particularly those host antiviral innate immune responses,are associated with the virulence of ASFV *** knockout of these genes does not impact viral replication,it does attenuate the virulence of ASFV in *** immunized with these live attenuated vaccine candidates can provide partial or complete *** on these findings,we propose a new concept that ASFV immunomodulatory genes involved in type I interferon(IFN)production,IFN-JAK-STAT signaling,inflammatory responses,cell death(involved in apoptosis,necrosis,and pyroptosis),and autophagy may be related to the pathogenicity of *** unbiased screening may identify more ASFV immunomodulatory or multifunctional genes,simplifying the confirmation of ASFV virulence-related *** line with these theories,we have identified MGF505-7R and H240R as key virulence genes determining the pathogenicity of the ASFV HLJ/18 *** of MGF505-7R,H240R alone or both attenuate the virulence of ASFV HLJ/18 in pigs,providing a paradigm for developing attenuated live vaccines from basic research results.

关键词： attenuated fever swine

Identification and characterization of human hematopoietic mesoderm

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Science China(Life Sciences) 2024年第2期67卷 320-331页

作者： Yuqi Wen Jingjing Zhao Runqing Zhang Fan Liu Xiaoyuan Chen Dan Wu Mengge Wang Cuicui Liu Pei Su Panpan Meng Yiyue Zhang Xin Gao Lu Wang Hongtao Wang Jiaxi Zhou State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood DiseasesHaihe Laboratory of Cell EcosystemInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300020China Tianjin Institutes of Health Science Tianjin 301600China CAMS Center for Stem cell Medicine PUMC Department of Stem Cell and Regenerative MedicineTianjin 300020China division of cell Developmental and Integrative BiologySchool of MedicineSouth China University of TechnologyGuangzhou 510006China

The embryonic mesoderm comprises heterogeneous cell subpopulations with distinct lineage *** is unclear whether a bias for the human hematopoietic lineage emerges at this early developmental *** this study,we integrated single-cell transcriptomic analyses of human mesoderm cells from embryonic stem cells and embryos,enabling us to identify and define the molecular features of human hematopoietic mesoderm(HM)cells biased towards hematopoietic *** discovered that BMP4 plays an essential role in HM specification and can serve as a marker for HM ***,BMP4 acts as a downstream target of HDAC1,which modulates the expression of BMP4 by deacetylating its *** of HDAC significantly enhances HM specification and promotes subsequent hematopoietic cell *** conclusion,our study identifies human HM cells and describes new mechanisms for human hematopoietic development.

关键词： hematopoietic mesoderm human pluripotent stem cells human embryos BMP4 HDAC1

Pandemic punch:SARS-CoV-2 hits pancreas

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1779-1780页

作者： Ninel Azoitei Sandra Heller Alexander Kleger Institute of Molecular Oncology and Stem cell Biology Ulm UniversityUlmGermany division of Interdisciplinary Pancreatology Clinic of Internal Medicine IUniversity Hospital UlmUlmGermany

The COVID-19 pandemic has profoundly impacted global health systems,revealing the extensive repercussions of SARS-CoV-2 beyond respiratory ***,traditionally considered a respiratory virus,SARS-CoV-2’s showcased the ability to target multiple organ systems including pancreas,an organ crucial for regulating blood sugar levels and aiding digestion.

关键词： pancreas respiratory traditionally

Cancer-associated fibroblasts express CD1d and activate invariant natural killer T cells under cellular stress

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cellular & Molecular immunology 2024年第1期21卷 91-94页

作者： Shengduo Pei Jonas Sjölund Yueyun Pan Kristian Pietras Mikael C.I.Karlsson Department of Microbiology Tumor and Cell BiologyKarolinska InstitutetStockholmSweden division of Translational Cancer Research Department of Laboratory MedicineLund University Cancer CentreLund UniversityLundSweden

Invariant natural killer T(iNKT)cells are part of the family of unconventional T cells,and they recognize glycolipid antigens presented on the MHC class I like molecule CD1^([1]).In humans there are five CD1 molecules named CD1a to CD1e,whereas mice use only CD1d for lipid ***,iNKT cells can elicit both cytotoxicity similarly to conventional CD8 T cells and secrete cytokines that influence the adaptive immune response including providing direct T cell help to B cells^([2]).In the context of tumors,they can use both release of granzyme B and use Fas-mediated mechanisms for killing of tumor *** iNKT cells use a restricted TCR repertoire and CD1 molecules are non-heterogenous the risk of graft vs host disease is limited and thus these T cells have been an attractive option for off the shelf immunotherapy to treat cancer^([3]).

关键词： killer CD1d Cancer

Protein synthesis,degradation,and energy metabolism in T cell immunity

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cellular & Molecular immunology 2022年第3期19卷 303-315页

作者： Julia M.Marchingo Doreen A.Cantrell cell signalling and immunology division School of Life SciencesUniversity of DundeeDundeeDD15EHUK

T cell activation,proliferation,and differentiation into effector and memory states involve massive remodeling of T cell size and molecular content and create a massive increase in demand for energy and amino *** synthesis is an energy-and resource-demanding process;as such,changes in T cell energy production are intrinsically linked to proteome *** this review,we discuss how protein synthesis and degradation change over the course of a T cell immune response and the crosstalk between these processes and T cell energy *** highlight how the use of high-resolution mass spectrometry to analyze T cell proteomes can improve our understanding of how these processes are regulated.

关键词： T lymphocyte Protein Translation Proteomics Immunometabolism Protein degradation