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Immunologic tumor microenvironment modulators for turning cold tumors hot

Cancer Communications 2024年第5期44卷 521-553页

作者： Gholam-Reza Khosravi Samaneh Mostafavi Sanaz Bastan Narges Ebrahimi Roya Safari Gharibvand Nahid Eskandari department of medical immunology School of MedicineIsfahan University of Medical SciencesIsfahanIran department of immunology Faculty of Medical SciencesTarbiat Modares UniversityTehranIran department of immunology School of MedicineAhvaz Jundishapur University of Medical SciencesAhvazIran

Tumors can be classified into distinct immunophenotypes based on the presence and arrangement of cytotoxic immune cells within the tumor microenvironment(TME).Hot tumors,characterized by heightened immune activity and responsiveness to immune checkpoint inhibitors(ICIs),stand in stark contrast to cold tumors,which lack immune infiltration and remain resistant to *** overcome immune evasion mechanisms employed by tumor cells,novel immunologic modulators have emerged,particularly ICIs targeting cytotoxic T-lymphocyte-associated protein 4.CTLA-4.and programmed cell death protein 1/programmed death-ligand 1(PD-1/PD-L1).These agents disrupt inhibitory signals and reactivate the immune system,transforming cold tumors into hot ones and promoting effective antitumor ***,challenges persist,including primary resistance to immunotherapy,autoimmune side effects,and tumor response *** these challenges requires innovative strategies,deeper mechanistic insights,and a combination of immune interventions to enhance the effectiveness of *** the landscape of cancer medicine,where immune cold tumors represent a formidable hurdle,understanding the TME and harnessing its potential to reprogram the immune response is *** review sheds light on current advancements and future directions in the quest for more effective and safer cancer treatment strategies,offering hope for patients with immune-resistant tumors.

关键词： cold tumor hot tumor immunologic modulator immunotherapy therapeutic strategy tumor microenvironment

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Role of ACLY in the development of gastric cancer under hyperglycemic conditions

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Quantitative Biology 2024年第1期12卷 100-116页

作者： Keran Sun Jingyuan Ning Keqi Jia Xiaoqing Fan Hongru Li Jize Ma Meiqi Meng Cuiqing Ma Lin Wei department of immunology Immunology Department of Hebei Medical UniversityShijiazhuangChina department of Pathology Pathology Department of the Fourth Hospital of Hebei Medical UniversityShijiazhuangChina

To investigate the impact of hyperglycemia on the prognosis of patients with gastric cancer and identify key molecules associated with high glucose levels in gastric cancer development,RNA sequencing data and clinical features of gastric cancer patients were obtained from The Cancer Genome Atlas(TCGA)*** glucose-related genes strongly associated with gastric cancer were identified using weighted gene co-expression network and differential analyses.A gastric cancer prognosis signature was constructed based on these genes and patients were categorized into high-and low-risk *** immune statuses of the two patient groups were *** citrate lyase(ACLY),a gene significantly related to the prognosis,was found to be upregulated upon high-glucose *** and molecular analyses confirmed high ACLY expression in gastric cancer tissues and *** Set Enrichment Analysis(GSEA)revealed the involvement of ACLY in cell cycle and DNA replication *** of ACLY affected the proliferation and migration of gastric cancer cells induced by high glucose *** findings suggest that ACLY,as a high glucose-related gene,plays a critical role in gastric cancer progression.

关键词： ACLY gastric cancer high glucose immune microenvironment

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Progress in gut microbiota-host interaction

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Science China(Life Sciences) 2024年第5期67卷 851-853页

作者： Changtao Jiang department of immunology School of Basic Medical SciencesNHC Key Laboratory of Medical ImmunologyPeking UniversityBeijing 100191China

Recently,the gut microbiota has been recognized as a novel endocrine organ in the human *** produces various bioactive metabolites and participates in metabolic *** addition,the gut microbiota is involved in the metab... 详细信息

关键词： metabolism drugs processes

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The anti-neoplastic effects of metformin modulate the acquired phenotype of fbroblast cells in the breast cancer-normal fbroblast co-culture system

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Oncology Research 2024年第3期32卷 477-487页

作者： SAMANEH MOSTAFAVI ZUHAIR MOHAMMAD HASSAN department of immunology Faculty of Medical SciencesTarbiat Modares UniversityTehranIran

Intracellular communications between breast cancer and fibroblast cells were reported to be involved in cancer proliferation,growth,and therapy *** hallmarks of cancer fibroblast interactions,consisting of caveolin 1(Cav1)and mono-carboxylate ransporter 4.MCT4.(metabolic coupling markers),along with IL-6,TGFB,and lactate secretion,are considered robust biomarkers predicting recurrence and *** order to promote a novel phenotype in normal fibroblasts,we predicted that breast cancer cells could be able to cause loss of Cavl and increase of MCT4.as well as elevate IL 6 and TGF in nearby nomal *** created a co culture model using breast cancer(4.1)and normal fibroblast(NIH3T3)cell lines cultured under specific experimental conditions in order to directly test our ***,we show that long-term co-culture of breast cancer cells and normal fibroblasts promotes loss of Cavl and gain of MCT4.in adjacent fibroblasts and increase lactate *** results were validated using the monoculture of each group separately as a *** this system,we show that me tformin inhibits IL-6 and TGFB secretion and re expresses Cavl in both ***,MCT4.and lactate stayed high after treatment with *** conclusion,our work shows that co-culture with breast cancer cells may cause signifcant alterations in the phenotype and secretion of normal ***,however,may change this state and affect fibroblasts'acquired ***,mitochondrial inhibition by metformin after 8 days of treatment,signi ficantly hinders tumor growth in mouse model of breast cancer.

关键词： Caveolin 1 Lactic acid Metformin NIH 3T3 cells Neoplasms

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Eosinophils promote CD8+ T cell memory generation to potentiate anti-bacterial immunity

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1230-1243页

作者： Jun Zhou Jiaqi Liu Bingjing Wang Nan Li Juan Liu Yanmei Han Xuetao Cao Institute of immunology Zhejiang University School of MedicineHangzhou 310058China National Key Laboratory of Immunity and Inflammation Institute of ImmunologyNaval Medical UniversityShanghai 200433China department of immunology Center for ImmunotherapyInstitute of Basic Medical SciencesPeking Union Medical CollegeChinese Academy of Medical SciencesBeijing 100005China Institute of immunology College of Life SciencesNankai UniversityTianjin 300071China

Memory CD8+T cell generation is crucial for pathogen elimination and effective vaccination against *** cellular and molecular circuitry that underlies the generation of memory CD8+T cells remains *** can modulate inflammatory allergic responses and interact with lymphocytes to regulate their functions in immune *** we report that eosinophils are required for the generation of memory CD8+T cells by inhibiting CD8+T cell ***-deficient mice display significantly impaired memory CD8+T cell response and weakened resistance against Listeria monocytogenes(L.m.)***,eosinophils secrete interleukin-4.IL-4.to inhibit JNK/Caspase-3 dependent apoptosis of CD8+T cells upon *** in ***,active eosinophils are recruited into the spleen and secrete more IL-4.to suppress CD8+T cell apoptosis during early stage of *** in *** transfer of wild-type(WT)eosinophils but not IL-4.deficient eosinophils into eosinophil-deficient mice could rescue the impaired CD8+T cell memory ***,our findings suggest that eosinophil-derived IL-4.promotes the generation of CD8+T cell memory and enhances immune defense against *** study reveals a new adjuvant role of eosinophils in memory T cell generation and provides clues for enhancing the vaccine potency via targeting eosinophils and related cytokines.

关键词： impaired immunity spleen

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Two distinct subpopulations of marginal zone B cells exhibit differential antibody-producing capacities and radioresistance

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Cellular & Molecular immunology 2024年第4期21卷 393-408页

作者： Sujin Lee Yeunjung Ko Hyun Woo Lee Won Joon Oh Hun Gi Hong Dinuka Ariyaratne Se Jin Im Tae Jin Kim department of immunology Graduate School of Basic Medical ScienceSungkyunkwan University School of MedicineSuwon16419Republic of Korea department of immunology and Molecular Medicine Faculty of Medical SciencesUniversity of Sri JayewardenepuraNugegodaSri Lanka Present address:immunology and Microbiology Graduate Program Baylor College of MedicineHoustonTX77030USA

Marginal zone(MZ)B cells,which are splenic innate-like B cells that rapidly secrete antibodies(Abs)against blood-borne pathogens,are composed of heterogeneous ***,we showed that MZ B cells can be divided into two distinct subpopulations according to their CD80 expression ***80^(high)MZ B cells exhibited greater Ab-producing,proliferative,and IL-10-secreting capacities than did CD80^(low)MZ B ***,CD80^(high)MZ B cells survived 2-Gy whole-body irradiation,whereas CD80^(low)MZ B cells were depleted by irradiation and then repleted with one month after *** of CD80^(low)MZ B cells led to accelerated development of type II collagen(CII)-induced arthritis upon immunization with bovine ***80^(high)MZ B cells exhibited higher expression of genes involved in proliferation,plasma cell differentiation,and the antioxidant ***80^(high)MZ B cells expressed more autoreactive B cell receptors(BCRs)that recognized double-stranded DNA or CII,expressed more immunoglobulin heavy chain sequences with shorter complementarity-determining region 3 sequences,and included more clonotypes with no N-nucleotides or with B-1a BCR sequences than CD80^(low)MZ B *** transfer experiments showed that CD21^(+)CD23^(+)transitional 2 MZ precursors preferentially generated CD80^(low)MZ B cells and that a proportion of CD80^(low)MZ B cells were converted into CD80^(high)MZ B cells;in contrast,CD80^(high)MZ B cells stably remained CD80^(high)MZ B *** summary,MZ B cells can be divided into two subpopulations according to their CD80 expression levels,Ab-producing capacity,radioresistance,and autoreactivity,and these findings may suggest a hierarchical composition of MZ B cells with differential stability and BCR specificity.

关键词： Marginal Zone B Cell CD80 Autoreactivity Radioresistance

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CD4.(+)T cells produce IFN-I to license cDC1s for induction of cytotoxic T-cell activity in human tumors

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Cellular & Molecular immunology 2024年第4期21卷 374-392页

作者： Xin Lei Daniël C.de Groot Marij J.P.Welters Tom de Wit Ellen Schrama Hans van Eenennaam Saskia J.Santegoets Timo Oosenbrug Annemarthe van der Veen Joris L.Vos Charlotte L.Zuur Noel F.C.C.de Miranda Heinz Jacobs Sjoerd H.van der Burg Jannie Borst Yanling Xiao department of immunology Leiden University Medical CenterLeidenThe Netherlands Oncode Institute Leiden University Medical CenterLeidenThe Netherlands department of Tumor Biology and immunology The Netherlands Cancer InstituteAmsterdamThe Netherlands department of medical Oncology Oncode InstituteLeiden University Medical CenterLeidenThe Netherlands IMMIOS B.V. OssThe Netherlands Division of medical Oncology The Netherlands Cancer InstituteAmsterdamThe Netherlands department of Otorhinolaryngology Leiden University medical Center LeidenThe Netherlands department of Pathology Leiden University Medical CenterLeidenThe Netherlands

CD4.(+)T cells can"help"or"license" conventional type 1 dendritic cells(cDC1s)to induce CD8^(+)cytotoxic T lymphocyte(CTL)anticancer responses,as proven in mouse *** recently identified cDC1s with a transcriptomic imprint of CD4.(+)T-cell help,specifically in T-cell-infiltrated human cancers,and these cells were associated with a good prognosis and response to PD-1-targeting ***,we delineate the mechanism of cDC1 licensing by CD4.(+)T cells in *** CD4.(+)T cells produce IFNβvia the STING pathway,which promotes MHC-I antigen(cross-)presentation by cDC1s and thereby improves their ability to induce CTL anticancer *** cooperation with CD4. ligand(L),IFNβalso optimizes the costimulatory and other functions of cDC1s required for CTL response ***-I-producing CD4.(+)T cells are present in diverse T-cell-infiltrated cancers and likely deliver“help”signals to CTLs locally,according to their transcriptomic profile and colocalization with“helped/licensed”cDCs and tumor-reactive CD8^(+)T *** agreement with this scenario,the presence of IFN-I-producing CD4.(+)T cells in the TME is associated with overall survival and the response to PD-1 checkpoint blockade in cancer patients.

关键词： CD4.(+)T-cell help cDC1 licensing IFN-I signaling CD4. costimulation (cross-)presentation CTL priming Tumor control

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Targeting carnitine palmitoyl transferase 1A(CPT1A)induces ferroptosis and synergizes with immunotherapy in lung cancer

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1675-1689页

作者： Lei Ma Chong Chen Chunxing Zhao Tong Li Lingyu Ma Jiayu Jiang Zhaojun Duan Qin Si Tsung-Hsien Chuang Rong Xiang Yunping Luo department of immunology Institute of Basic Medical SciencesChinese Academy of Medical SciencesSchool of Basic MedicinePeking Union Medical CollegeBeijing 100005China Collaborative Innovation Center for Biotherapy Institute of Basic Medical SciencesChinese Academy of Medical SciencesSchool of Basic MedicinePeking Union Medical CollegeBeijing 100005China department of Lung Cancer Surgery Tianjin Medical University General HospitalTianjin 300052China immunology Research Center National Health Research InstitutesZhunanMiaoliTaiwanROC department of immunology Nankai UniversityTianjin 300071China

Despite the successful application of immune checkpoint therapy,no response or recurrence is typical in lung *** stem cells(CSCs)have been identified as a crucial player in immunotherapy-related ***,a form of cell death driven by iron-dependent lipid peroxidation,is highly regulated by cellular metabolism remolding and has been shown to have synergistic effects when combined with *** adaption of CsCs drives tumor resistance,yet the mechanisms of their ferroptosis defense in tumor immune evasion remain ***,through metabolomics,transcriptomics,a lung epithelialspecific Cptla-knockout mouse model,and clinical analysis,we demonstrate that CPT1A,a key rate-limiting enzyme of fatty acid oxidation,acts with L-carnitine,derived from tumor-associated macrophages to drive ferroptosis-resistance and CD8^(+)T cells inactivation in lung ***,CPT1A restrains ubiquitination and degradation of c-Myc,while c-Myc transcriptionally activates CPT1A *** CPT1A/c-Myc positive feedback loop further enhances the cellular antioxidant capacity by activating the NRF2/GPX4.system and reduces the amount of phospholipid polyunsaturated fatty acids through ACSL4.downregulating,thereby suppressing ferroptosis in ***,targeting CPT1A enhances immune checkpoint blockadeinduced anti-tumor immunity and tumoral ferroptosis in tumor-bearing *** results illustrate the potential of a mechanismguided therapeutic strategy by targeting a metabolic vulnerability in the ferroptosis of CsCs to improve the efficacy of lung cancer immunotherapy.

关键词： immunotherapy metabolism peroxidation

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Resurgence of measles virus infection in an eliminated country, Sri Lanka

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Asian Pacific Journal of Tropical Medicine 2024年第5期17卷 208-213页

作者： Merennage Anusha Yasanthi Fernando Gankandage Prabhath Chathuranga Kaanthaka Gunaradha Abeygunasekara Dedunu Dias Weligamage Janaki Indira Abeynayake department of medical Microbiology and immunology Faculty of MedicineUniversity of ColomboSri Lanka department of Virology Medical Research InstituteColombo 08Sri Lanka department of medical Administration Medical Research InstituteColombo 08Sri Lanka

Objective:To describe the situation of measles in Sri Lanka from May to November,2023 and to define the role of virology laboratory towards case confirmation and epidemiological and genetic characterization of the ***:This retrospective study analyzed all samples tested for measles from 1st of May to 30th of November,2023 at National Measles Rubella Laboratory,Sri *** to the World Health Organization(WHO)algorithm,serum and oropharyngeal/nasopharyngeal swabs were tested with WHO recommended kits for anti-measles IgM and measles virus specific RNA,*** RNA positive samples were sequenced at reference laboratory,*** of sequencing data and construction of phylogenetic tree were carried out at National Measles Rubella *** was analyzed using descriptive ***:Of the total 1132 serum samples and 4.7 oropharyngeal/nasopharyngeal swabs from 1326 patients,657(4..5%)patients were confirmed as measles by anti-measles IgM,measles virus specific RNA or ***(55.6%,n=365)and the age group from>20 to≤30 years(33.0%,n=217)predominated positive *** provinces reported measles positive *** samples sequenced(100%,n=4.)were genotype D8 with 95.2%(n=4.)bearing *** ***:We described resurgence of measles in an eliminated country,confirming the genotype to be D8,one of the two genotypes currently circulating ***,the study strongly convinced the importance of a strengthened virological surveillance system in an eliminated country,despite its eliminated status.

关键词： Measles elimination Resurgence of measles Sri Lanka Genotype D8 National Measles Rubella Laboratory

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Emergency department management of acute agitation in the reproductive age female and pregnancy

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World Journal of Emergency Medicine 2024年第2期15卷 83-90页

作者： Ariella Gartenberg Kayla Levine Alexander Petrie department of Emergency Medicine Jacobi Medical Center and Montefiore Medical CenterNY 10461USA department of Psychiatry and Behavioral Sciences Albert Einstein College of Medicine and Montefiore Medical CenterNY 10461USA department of Emergency Medicine Jacobi Medical Center and North Central Bronx HospitalNY 10461USA

BACKGROUND:Agitation is a common presentation within emergent departments(EDs).Agitation during pregnancy should be treated as an obstetric emergency,as the distress may jeopardize both the patient and *** safety of psychotropic medications in the reproductive age female has not been well *** review aimed to explore a summary of general agitation recommendations with an emphasis on ED management of agitation during ***:A literature review was conducted to explore the pathophysiology of acute agitation and devise a preferred treatment plan for ED management of acute agitation in the reproductive age or pregnant ***:While nonpharmacological management is preferred,ED visits for agitation often require medical *** should be selected based on the etiology of agitation and the clinical setting to avoid major adverse *** effects are common in pregnant *** mild to moderate agitation in pregnancy,diphenhydramine is an effective sedating agent with minimal adverse *** moderate to severe agitation,high-potency typical psychotropics are preferred due to their neutral effects on *** has become the most frequently utilized psychotropic for agitation during *** generation psychotropics are often utilized as second-line therapy,including *** and ketamine have demonstrated adverse fetal ***:While randomized control studies cannot be ethically conducted on pregnant patients requiring sedation,animal models and epidemiologic studies have demonstrated the effects of psychotropic medication exposure in *** the fetal risk associated with multiple doses of psychotropic medications remains unknown,weighing the risks and benefits of each agent,while utilizing the lowest effective dose remains critical in the treatment of acute agitation within the EDs.

关键词： Agitation Pregnancy Haloperidol Ketamine Benzodiazepines

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