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Expanded clinical-grade NK cells exhibit stronger effects than primary NK cells against HCMV infection

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Cellular & Molecular Immunology 2023年第8期20卷 895-907页

作者： Qian-Nan Shang Xing-Xing Yu Zheng-Li Xu Yu-Hong Chen Ting-Ting Han Yuan-Yuan Zhang Meng Lv Yu-Qian Sun Yu Wang Lan-Ping Xu Xiao-Hui Zhang Xiang-Yu Zhao Xiao-Jun Huang Peking University People’s Hospital Peking University Institute of HematologyNational Clinical Research Center for Hematologic DiseaseBeijing Key Laboratory of Hematopoietic Stem Cell TransplantationPeking UniversityBeijingChina Peking-Tsinghua center for Life Sciences Academy for Advanced Interdisciplinary StudiesPeking UniversityBeijingChina

Cytomegalovirus (CMV) reactivation remains a common complication and leads to high mortality in patients who undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT). Early natural killer (NK) cell reconstitution may protect against the development of human CMV (HCMV) infection post-HSCT. Our previous data showed that ex vivo mbIL21/4-1BBL-expanded NK cells exhibited high cytotoxicity against leukemia cells. Nevertheless, whether expanded NK cells have stronger anti-HCMV function is unknown. Herein, we compared the anti-HCMV functions of ex vivo expanded NK cells and primary NK cells. Expanded NK cells showed higher expression of activating receptors, chemokine receptors and adhesion molecules;stronger cytotoxicity against HCMV-infected fibroblasts;and better inhibition of HCMV propagation in vitro than primary NK cells. In HCMV-infected humanized mice, expanded NK cell infusion resulted in higher NK cell persistence and more effective tissue HCMV elimination than primary NK cell infusion. A clinical cohort of 20 post-HSCT patients who underwent adoptive NK cell infusion had a significantly lower cumulative incidence of HCMV infection (HR = 0.54, 95% CI = 0.32–0.93, p = 0.042) and refractory HCMV infection (HR = 0.34, 95% CI = 0.18–0.65, p = 0.009) than controls and better NK cell reconstitution on day 30 post NK cell infusion. In conclusion, expanded NK cells exhibit stronger effects than primary NK cells against HCMV infection both in vivo and in vitro.

关键词： Allogeneic haematopoietic stem cell transplantation Natural killer cells Human cytomegalovirus infection Adoptive infusion

'nAb'the self-reactive activity in the COVID-19 combat

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Signal Transduction and Targeted Therapy 2021年第4期6卷 1077-1078页

作者： Madhusudhanan Narasimhan Lenin Mahimainathan Alagarraju Muthukumar Department of pathology University of Texas Southwestern Medical CenterDallasTXUSA

The recent article in Cell by Kreye et al.1 discovered that non-self-reactive-neutralizing antibody(ns-nAb)could be an effective way to combat SARS-CoV-2 *** observations provide new perspectives for therapeutic antib... 详细信息

关键词： al. reactive neutral

PREPARATION AND CHARACTERIZATION OF MONOCLONAL ANTIBODY AGAINST HUMAN TELOME RASE REVERSE TRANSCRIPTASE

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Chinese Medical Sciences Journal 2003年第3期18卷 143-149页

作者：王俊梅张波杨邵敏韩继生李冰思侯琳 Department of pathology Health Science Center of Peking UniversityBeijing 100083

*** develop monoclonal antibodies again st the catalytic subunit of human telomerase reverse transcriptasefor i ts expression detection of human ***.A dominant epitope in hTERT was automatically synthesized based on Fmoc method,and was used to immuni ze Balb/c *** were generated and screened by ELISA for specific mo noclonal antibodies,and the characterization was performed by Western blotting and immunohistochemical *** heavy chain variable region of antibody wa s cloned by RT-PCR and *** peptide hTERT 7 was synthesized and confirmed by MALDI-TOF-MS and HPLC *** hybr idoma cell line secreting anti-hTERT 7 antibodies designated as M2was established after primary screening and cons equent 3rounds of limited dilution.M2was IgG1in *** competi-tive assay showed that the M2antibody was hTERT 7-specific,and the affinity constant was about 1×10 6 mol-1 .The antibody reacted with cell extracts from HeLa cancer cells but not wi th those from normal2BS cells in ELISA *** in situ staining of immunohis tochemistry,the positive staining presented in the nuclear compartment of HeLa ,while2BS was *** heavy chain variable region from M2re-vealed tha t the monoclonal antibody was mouse *** developed mouse mon oclonal antibody is hTERT-specific and able to recognize native cellular hTERT in ELISA and immunohistochemistry,which makes the immuno-detection of telom-e rase hTERT expression in cancer cells or tissues possible.

关键词： telomerase human telomerase reverse tran scriptase monoclonal antibody

Th2 polarization in target organs is involved in the alleviation of pathological damage mediated by transplanting granulocyte colony-stimulating factor-primed donor T cells

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Science China(Life Sciences) 2021年第7期64卷 1087-1096页

作者： Yang Zhoui Leqing Cao Huidong Guo Yan Hong Ming Wang Ke Wang Xiaojun Huang Yingjun Chang Peking University People's Hospital Peking University Institute of HematologyNational Clinical Research Center for Hematologic DiseaseBeijing Key Laboratory of HSCTPeking UniversityBeijing 100044China Peking-Tsinghua center for Life Sciences Academy for Advanced Interdisciplinaiy StudiesPeking UniversityBeijing 100044China

Acute graft-versus-host disease(a GVHD)is caused by allo-activated donor T cells infiltrating target *** a regulator of immune function,granulocyte colony-stimulating factor(G-CSF)has been demonstrated to relieve the a GVHD ***,the role of G-CSF-primed donor Tcells in specific target organs is still *** this study,we employed a classical MHC-mismatched transplantation mouse model(C57BL/6 into BALB/c)and found that recipient mice transplanted with GCSF-primed T cells exhibited prolonged survival compared with that of the PBS-treated *** protective function against GVHD mediated by G-CSF-primed donor T cells was further confirmed by decreased clinical and pathological scores in this a GVHD mouse model,especially in the lung and ***,we found that Tcells polarized towards Th2 cells and regulatory T cells were increased in specific target *** addition,G-CSF treatment inhibited inducible co-stimulator(ICOS)expression and increased the expression of tolerance-related genes in recipient *** study provides new insight into the immune regulatory effects of G-CSF on T cell-mediated a GVHD,especially for its precise regulation in GVHD target organs.

关键词： granulocyte colony-stimulating factor graft-versus-host disease mouse model Th2 polarization

Azathioprine does not reduce adenoma formation in a mouse model of sporadic intestinal tumorigenesis

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World Journal of Gastroenterology 2014年第44期20卷 16683-16689页

作者： Mattheus CB Wielenga Jooske F van Lidth de Jeude Sanne L Rosekrans Alon D Levin Monique Schukking Geert RAM D'Haens Jarom Heijmans Marnix Jansen Vanesa Muncan Gijs R van den Brink Tytgat Institute for Liver and Intestinal Research and Department of Gastroenterology and Hepatology Academic Medical Center Department of pathology Academic Medical Center

AIM: To investigate if azathioprine could reduce adenoma formation in ApcMin/+, a mouse model of sporadic intestinal tumorigenesis.

关键词： Azathioprine Thiopurine Intestinal adenoma Polyp ApcMin Chemoprevention Lymphoma Colon cancer

Vulvar granular cell tumor

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World Journal of Clinical Cases 2013年第4期1卷 149-151页

作者： Michel E Rivlin G Rodney Meeks Mohamed A Ghafar Jack R Lewin Departments of Obstetrics Gynecology and Pathology University of Mississippi Medical Center

Granular cell tumors are rare,usually benign,soft tissue neoplasms of neural *** occur more often in females than males,the peak age incidence is in the fourth through fifth *** can occur anywhere in the body with up to 15% situated in the *** commonest presentation is as an asymptomatic *** findings are usually sufficient,but immunohistochemistry can also be helpful in confirming the *** vulvar tumors are benign in 98% of cases with 2% reported as *** this case report we describe a woman with a granular cell tumor confirmed by biopsy who underwent excision of the mass but with focal extension to the resection margin on *** recommendation of re-excision was *** it is not uncommon with these tumors to find groups of tumor cells extending beyond the macroscopic limits of growth,we conclude that it is advisable to have margins assessed intraoperatively by frozen section such that further excision can be performed for positive *** patient has been followed for 18 mo without recurrence,should the tumor recur,re-excision,with frozen section control,is *** rates are reported as 2%-8% with clear margins and 20% with positive margins.

关键词： Granular cell tumor Vulvar tumor Vulvar neoplasm

Human papillomavirus-related squamous cell carcinoma of the anal canal with papillary features

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World Journal of Gastroenterology 2015年第7期21卷 2210-2213页

作者： Marino E Leon Rania Shamekh Domenico Coppola Department of Anatomic pathology H. Lee Moffitt Cancer Center and Research Institute Department of pathology and Cell Biology University of South Florida

Human papillomavirus(HPV)related squamous cell carcinoma(SCC)involving the anal canal is a well-known carcinoma associated with high-risk types of *** SCC with papillary morphology(papillary SCC)has been described in the *** describe,for the first time,a case of anal HPV-related squamous carcinoma with papillary *** tumor arose from the anal *** biopsies revealed a superficially invasive SCCwith prominent papillary features and associated in situ *** tumor cells were positive for p16 and were also positive for high-risk types of HPV using chromogenic in situ *** findings are consistent with a HPV-related SCC of the anal canal with papillary *** tumor shows histologic features similar to a papillary HPV-related SCC of the *** studies are needed to characterize these lesions.

关键词： Anus Squamous cell carcinoma Papillary Human papil

Glucocorticoid and glycolysis inhibitors cooperatively abrogate acute graft-versus-host disease

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Science China(Life Sciences) 2023年第3期66卷 528-544页

作者： Qi Wen Zheng-Li Xu Yu Wang Meng Lv Yang Song Zhong-Shi Lyv Tong Xing Lan-Ping Xu Xiao-Hui Zhang Xiao-Jun Huang Yuan Kong Peking University People's Hospital Peking University Institute of HematologyNational Clinical Research Center for Hematologic DiseaseBeijing Key Laboratory of Hematopoietic Stem Cell TransplantationCollaborative Innovation Center of HematologyPeking UniversityBeijing 100044China Peking-Tsinghua center for Life Sciences Academy for Advanced Interdisciplinary StudiesPeking UniversityBeijing 100044China

Although glucorticosteroids(GCs)are the standard first-line therapy for acute graft-versus-host disease(a Gv HD),nearly 50%of a Gv HD patients have no response to *** role of T cell metabolism in murine a Gv HD was recently ***,whether GCs and metabolism regulators could cooperatively suppress T cell alloreactivity and ameliorate a Gv HD remains to be *** glycolysis,characterized by elevated 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3(PFKFB3),and higher rates of glucose consumption and lactate production were found in Tcells from a Gv HD *** upregulation of PFKFB3 induced T cell proliferation and differentiation into proinflammatory *** a humanized mouse model,PFKFB3-overexpressing or PFKFB3-silenced T cells aggravated or prevented a Gv HD,***,our integrated data from patient samples in vitro,in a humanized xenogeneic murine model of a Gv HD and graft-versus-leukaemia(GVL)demonstrate that GCs combined with a glycolysis inhibitor could cooperatively reduce the alloreactivity of T cells and ameliorate a Gv HD without loss of GVL ***,the current study indicated that glycolysis is critical for T cell activation and induction of human a Gv ***,the regulation of glycolysis offers a potential pathogenesis-oriented therapeutic strategy for a Gv HD *** combined with glycolysis inhibitors promises to be a novel first-line combination therapy for a Gv HD patients.

关键词： allogeneic haematopoietic stem cell transplantation graft versus host disease human T cells glycolysis

Blastomas of the digestive system in adults:A review

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World Journal of Gastrointestinal Surgery 2024年第4期16卷 1030-1042页

作者： Yu Liu Tony El Jabbour Jonathan Somma Yukihiro Nakanishi Saverio Ligato Hwajeong Lee Zhi-Yan Fu Department of pathology LSU Health Sciences Center School of MedicineNew OrleansLA 70112United States Department of pathology Hartford HealthCareHartfordCT 06102United States Department of pathology Moffitt Cancer CenterTampaFL 33612United States Department of pathology and Laboratory Medicine Albany Medical CenterAlbanyNY 12208United States

Blastomas,characterized by a mixture of mesenchymal,epithelial,and undifferentiated blastematous components,are rare malignant neoplasms originating from precursor blast *** review focuses on digestive system blastomas in adult patients,including gastroblastoma,hepatoblastoma,and *** is a biphasic,epitheliomesenchymal tumor,with only sixteen cases reported to *** addition to the characteristic histology,metastasisassociated lung adenocarcinoma transcript 1-glioma-associated oncogene homolog 1 gene fusion is typical,although recently novel ewing sarcoma breakpoint region 1-c-terminal binding protein 1 and patched 1-glioma-associated oncogene homolog 2 fusions have been *** is exceptionally rare in adults and can show a variety of histologic patterns which may cause diagnostic ***,primarily a pediatric tumor,displays acinar differentiation and squamoid nests with other lines of differentiation also present,especially *** approaches for these blastomas include a combination of imaging modalities,histopathological examination,and molecular *** treatment generally involves surgical resection,which may be supplemented by chemotherapy or radiotherapy in some *** vary with gastroblastoma generally showing favorable outcomes post-surgery whereas hepatoblastoma and pancreatoblastoma often have poorer outcomes,particularly in the setting of *** review highlights the complexity of diagnosing and managing these rare adult blastomas as well as the need for ongoing research to better understand their pathogenesis and improve treatment strategies.

关键词： Adult blastomas Gastroblastoma Hepatoblastoma Pancreatoblastoma Digestive system