Clinical & Translational Immunology最新文献

{"title":"Plasma EBV quantification is associated with the efficacy of immune checkpoint blockade and disease monitoring in patients with primary pulmonary lymphoepithelioma-like carcinoma","authors":"Yu-Min Zhong,&nbsp;Ji Chen,&nbsp;Jie Jiang,&nbsp;Wen-Bin Zhou,&nbsp;Ling-Ling Gao,&nbsp;Shui-Lian Zhang,&nbsp;Wen-Qing Yan,&nbsp;Yu Chen,&nbsp;Dong-Kun Zhang,&nbsp;Dan-Xia Lu,&nbsp;Zhi-Yi Lv,&nbsp;Zhi Xie,&nbsp;Ying Huang,&nbsp;Wei-Bang Guo,&nbsp;Bin-Chao Wang,&nbsp;Jin-Ji Yang,&nbsp;Xue-Ning Yang,&nbsp;Yi-Long Wu,&nbsp;Xu-Chao Zhang","doi":"10.1002/cti2.1515","DOIUrl":"https://doi.org/10.1002/cti2.1515","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Primary pulmonary lymphoepithelioma-like carcinoma (PLELC) is a subtype of lung carcinoma associated with the Epstein–Barr virus (EBV). The clinical predictive biomarkers of immune checkpoint blockade (ICB) in PLELC require further investigation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We prospectively analysed EBV levels in the blood and immune tumor biomarkers of 31 patients with ICB-treated PLELC. Viral <i>EBNA-1</i> and <i>BamHI-W</i> DNA fragments in the plasma were quantified in parallel using quantitative polymerase chain reaction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Progression-free survival (PFS) was significantly longer in <i>EBNA-1</i> high or <i>BamHI-W</i> high groups. A longer PFS was also observed in patients with both high plasma <i>EBNA-1</i> or <i>BamHI-W</i> and PD-L1 ≥ 1%. Intriguingly, the tumor mutational burden was inversely correlated with <i>EBNA-1</i> and <i>BamHI-W</i>. Plasma EBV load was negatively associated with intratumoral CD8⁺ immune cell infiltration. Dynamic changes in plasma EBV DNA level were in accordance with the changes in tumor volume. An increase in EBV DNA levels during treatment indicated molecular progression that preceded the imaging progression by several months.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Plasma EBV DNA could be a useful and easy-to-use biomarker for predicting the clinical activity of ICB in PLELC and could serve to monitor disease progression earlier than computed tomography imaging.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 6","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1515","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141245979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineered CAR-T cells targeting the non-functional P2X purinoceptor 7 (P2X7) receptor as a novel treatment for ovarian cancer","authors":"Veronika Bandara,&nbsp;Victoria M Niktaras,&nbsp;Vasiliki J Willett,&nbsp;Hayley Chapman,&nbsp;Noor A Lokman,&nbsp;Anne M Macpherson,&nbsp;Silvana Napoli,&nbsp;Batjargal Gundsambuu,&nbsp;Jade Foeng,&nbsp;Timothy J Sadlon,&nbsp;Justin Coombs,&nbsp;Shaun R McColl,&nbsp;Simon C Barry,&nbsp;Martin K Oehler,&nbsp;Carmela Ricciardelli","doi":"10.1002/cti2.1512","DOIUrl":"https://doi.org/10.1002/cti2.1512","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Recent studies have identified expression of the non-functional P2X7 (nfP2X7) receptor on various malignant cells including ovarian cancer, but not on normal cells, which makes it a promising tumour-associated antigen candidate for chimeric antigen receptor (CAR)-T-cell immunotherapies. In this study, we assessed the cytotoxic effects of nfP2X7-CAR-T cells on ovarian cancer using <i>in vitro</i> and <i>in vivo</i> models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We evaluated the effects of nfP2X7-CAR-T cells on ovarian cancer cell lines (SKOV-3, OVCAR3, OVCAR5), normal peritoneal cells (LP-9) and primary serous ovarian cancer cells derived from patient ascites <i>in vitro</i> using monolayer and 3D spheroid assays. We also evaluated the effects of nfP2X7-CAR-T cells on patient-derived tissue explants, which recapitulate an intact tumour microenvironment. In addition, we investigated the effect of nfP2X7-CAR-T cells <i>in vivo</i> using the OVCAR-3 xenograft model in NOD-scid IL2Rγnull (NSG) mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our study found that nfP2X7-CAR-T cells were cytotoxic and significantly inhibited survival of OVCAR3, OVCAR5 and primary serous ovarian cancer cells compared with un-transduced CD3⁺ T cells <i>in vitro</i>. However, no significant effects of nfP2X7-CAR-T cells were observed for SKOV3 or normal peritoneal cells (LP-9) cells with low P2X7 receptor expression. Treatment with nfP2X7-CAR-T cells increased apoptosis compared with un-transduced T cells in patient-derived explants and correlated with CD3 positivity. Treatment with nfP2X7-CAR-T cells significantly reduced OVCAR3 tumour burden in mice compared with un-transduced CD3 cells for 7–8 weeks.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study demonstrates that nfP2X7-CAR-T cells have great potential to be developed as a novel immunotherapy for ovarian cancer.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1512","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141091440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From intramuscular to nasal: unleashing the potential of nasal spray vaccines against coronavirus disease 2019","authors":"Ge Jin,&nbsp;Runze Wang,&nbsp;Yi Jin,&nbsp;Yingqiu Song,&nbsp;Tianlu Wang","doi":"10.1002/cti2.1514","DOIUrl":"https://doi.org/10.1002/cti2.1514","url":null,"abstract":"<p>Coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected 700 million people worldwide since its outbreak in 2019. The current pandemic strains, including Omicron and its large subvariant series, exhibit strong transmission and stealth. After entering the human body, the virus first infects nasal epithelial cells and invades host cells through the angiotensin-converting enzyme 2 receptor and transmembrane serine protease 2 on the host cell surface. The nasal cavity is an important body part that protects against the virus. Immunisation of the nasal mucosa produces immunoglobulin A antibodies that effectively neutralise viruses. Saline nasal irrigation, a type of physical therapy, can reduce the viral load in the nasal cavity and prevent viral infections to some extent. As a commonly used means to fight SARS-CoV-2, the intramuscular (IM) vaccine can induce the human body to produce a systemic immune response and immunoglobulin G antibody; however, the antibody is difficult to distribute to the nasal mucosa in time and cannot achieve a good preventive effect. Intranasal (IN) vaccines compensate for the shortcomings of IM vaccines, induce mucosal immune responses, and have a better effect in preventing infection. In this review, we discuss the nasal defence barrier, the harm caused by SARS-CoV-2, the mechanism of its invasion into host cells, nasal cleaning, IM vaccines and IN vaccines, and suggest increasing the development of IN vaccines, and use of IN vaccines as a supplement to IM vaccines.</p>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1514","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141069092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterisation of novel influenza-derived HLA-B*18:01-restricted epitopes","authors":"Samuel Liwei Leong,&nbsp;Lawton Murdolo,&nbsp;Janesha C Maddumage,&nbsp;Marios Koutsakos,&nbsp;Katherine Kedzierska,&nbsp;Anthony W Purcell,&nbsp;Stephanie Gras,&nbsp;Emma J Grant","doi":"10.1002/cti2.1509","DOIUrl":"https://doi.org/10.1002/cti2.1509","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Seasonal influenza viruses cause roughly 650 000 deaths annually despite available vaccines. CD8⁺ T cells typically recognise influenza-derived peptides from internal structural and non-structural influenza proteins and are an attractive avenue for future vaccine design as they could reduce the severity of disease following infection with diverse influenza strains. CD8⁺ T cells recognise peptides presented by the highly polymorphic Human Leukocyte Antigens class I molecules (HLA-I). Each HLA-I variant has distinct peptide binding preferences, representing a significant obstacle for designing vaccines that elicit CD8⁺ T cell responses across broad populations. Consequently, the rational design of a CD8⁺ T cell-mediated vaccine would require the identification of highly immunogenic peptides restricted to a range of different HLA molecules.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Here, we assessed the immunogenicity of six recently published novel influenza-derived peptides identified by mass-spectrometry and predicted to bind to the prevalent HLA-B*18:01 molecule.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Using CD8⁺ T cell activation assays and protein biochemistry, we showed that 3/6 of the novel peptides were immunogenic in several HLA-B*18:01⁺ individuals and confirmed their HLA-B*18:01 restriction. We subsequently compared CD8⁺ T cell responses towards the previously identified highly immunogenic HLA-B*18:01-restricted NP₂₁₉ peptide. Using X-ray crystallography, we solved the first crystal structures of HLA-B*18:01 presenting immunogenic influenza-derived peptides. Finally, we dissected the first TCR repertoires specific for HLA-B*18:01 restricted pathogen-derived peptides, identifying private and restricted repertoires against each of the four peptides.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Overall the characterisation of these novel immunogenic peptides provides additional HLA-B*18:01-restricted vaccine targets derived from the Matrix protein 1 and potentially the non-structural protein and the RNA polymerase catalytic subunit of influenza viruses.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1509","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140907042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of extremely preterm birth on cytokine and chemokine responses induced by T-cell activation during infancy","authors":"Dhanapal Govindaraj,&nbsp;Georg Bach Jensen,&nbsp;Khaleda Rahman Qazi,&nbsp;Eva Sverremark-Ekström,&nbsp;Thomas Abrahamsson,&nbsp;Maria C Jenmalm","doi":"10.1002/cti2.1510","DOIUrl":"https://doi.org/10.1002/cti2.1510","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Extremely preterm (EPT; gestational week &lt; 28 + 0, &lt; 1000 g) neonates are vulnerable to infections and necrotising enterocolitis, important contributors to mortality and morbidity. However, knowledge regarding their immune maturation remains limited. We here investigated the longitudinal development of functional T-cell capacity in EPT infants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Peripheral blood mononuclear cells were isolated at 14th and 28th day (D) and at gestational week 36 + 0 (Gw36) from EPT infants, participated in a randomised, double-blind, placebo-controlled study of <i>Lactobacillus reuteri</i> DSM 17938 probiotic supplementation. Blood collected from 25 full-term (FT) infants at D14 was used as control. The secretion of immune mediators was determined through comprehensive Luminex panels after stimulation with human T-cell activator CD3/CD28 beads.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The levels of many mediators were low in EPT infants at D14, whereas the secretion of several chemokines was higher in EPT than in FT infants. Furthermore, Th2:Th1 cytokine ratios were higher in EPT than in FT infants. Progressively elevated secretion of, for example, IFN-γ, TNF and IL-17A in EPT infants was observed from D14 to D28 and then at Gw36. Elevated levels were observed for many proinflammatory mediators at D28. Probiotic supplementation or perinatal factors (e.g. clinical chorioamnionitis, preeclampsia and delivery mode) did not influence the cytokine and chemokine responses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Immune mediators induced by T-cell activation in EPT infants were mainly reduced at D14 and Th2 skewed compared to those in FT infants, but mostly recovered at Gw36, indicating immune maturation. Increased proinflammatory responses at D28 may be related to the heightened risk of severe immune-associated complications seen in EPT infants.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1510","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140907041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maintenance of caecal homeostasis by diverse adaptive immune cells in the rhesus macaque","authors":"Xaquin Castro Dopico,&nbsp;Mariia Guryleva,&nbsp;Marco Mandolesi,&nbsp;Martin Corcoran,&nbsp;Jonathan M Coquet,&nbsp;Ben Murrell,&nbsp;Gunilla B Karlsson Hedestam","doi":"10.1002/cti2.1508","DOIUrl":"https://doi.org/10.1002/cti2.1508","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>The caecum bridges the small and large intestine and plays a front-line role in discriminating gastrointestinal antigens. Although dysregulated in acute and chronic conditions, the tissue is often overlooked immunologically.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To address this issue, we applied single-cell transcriptomic-V(D)J sequencing to FACS-isolated CD45⁺ caecal patch/lamina propria leukocytes from a healthy (5-year-old) female rhesus macaque <i>ex vivo</i> and coupled these data to VDJ deep sequencing reads from haematopoietic tissues.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found caecal NK cells and ILC3s to co-exist with a spectrum of effector T cells partially derived from <i>SOX4</i>⁺ recent thymic emigrants. Tolerogenic Vγ8Vδ1-T cells, plastic CD4⁺ T helper cells and <i>GZMK</i>⁺<i>EOMES</i>⁺ and <i>TMIGD2</i>⁺ tissue-resident memory CD8⁺ T cells were present and differed metabolically. An <i>IL13</i>⁺<i>GATA3</i>⁺ Th₂ subset expressing eicosanoid pathway enzymes was accompanied by <i>IL1RL1</i>⁺<i>GATA3</i>⁺ regulatory T cells and a minor proportion of IgE⁺ plasma cells (PCs), illustrating tightly regulated type 2 immunity devoid of ILC2s. In terms of B lymphocyte lineages, caecal patch antigen-presenting memory B cells sat alongside germinal centre cells undergoing somatic hypermutation and differentiation into <i>IGF1</i>⁺ PCs. Prototypic gene expression signatures decreased across PC clusters, and notably, expanded IgA clonotypes could be traced in VDJ deep sequencing reads from additional compartments, including the bone marrow, supporting that these cells contribute a steady stream of systemic antibodies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The data advance our understanding of caecal immunological function, revealing processes involved in barrier maintenance and molecular networks relevant to disease.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1508","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140818974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimisation of a primary human CAR-NK cell manufacturing pipeline","authors":"Aline Pfefferle,&nbsp;Julian Contet,&nbsp;Kahlia Wong,&nbsp;Charlotte Chen,&nbsp;Els Verhoeyen,&nbsp;Chloe K Slichter,&nbsp;Kimberly S Schluns,&nbsp;Joseph Cursons,&nbsp;Richard Berry,&nbsp;Iva Nikolic,&nbsp;Jai Rautela,&nbsp;Nicholas D Huntington","doi":"10.1002/cti2.1507","DOIUrl":"https://doi.org/10.1002/cti2.1507","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Autologous chimeric antigen receptor (CAR) T-cell therapy of B-cell malignancies achieves long-term disease remission in a high fraction of patients and has triggered intense research into translating this successful approach into additional cancer types. However, the complex logistics involved in autologous CAR-T manufacturing, the compromised fitness of patient-derived T cells, the high rates of serious toxicities and the overall cost involved with product manufacturing and hospitalisation have driven innovation to overcome such hurdles. One alternative approach is the use of allogeneic natural killer (NK) cells as a source for CAR-NK cell therapy. However, this source has traditionally faced numerous manufacturing challenges.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To address this, we have developed an optimised expansion and transduction protocol for primary human NK cells primed for manufacturing scaling and clinical evaluation. We have performed an in-depth comparison of primary human NK cell sources as a starting material by characterising their phenotype, functionality, expansion potential and transduction efficiency at crucial timepoints of our CAR-NK manufacturing pipeline.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified adult peripheral blood-derived NK cells to be the superior source for generating a CAR-NK cell product because of a higher maximum yield of CAR-expressing NK cells combined with potent natural, as well as CAR-mediated anti-tumor effector functions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our optimised manufacturing pipeline dramatically improves lentiviral transduction efficiency of primary human NK cells. We conclude that the exponential expansion pre- and post-transduction and high on-target cytotoxicity make peripheral blood-derived NK cells a feasible and attractive CAR-NK cell product for clinical utility.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1507","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140818975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chitinase 3-like 1 expression associated with lymphatic metastasis and prognosis in urothelial carcinoma of the bladder","authors":"Bo Wang,&nbsp;Ke Chen,&nbsp;Mingchao Gao,&nbsp;Xi Sun,&nbsp;Wang He,&nbsp;Junyu Chen,&nbsp;Wenjuan Yang,&nbsp;Tenghao Yang,&nbsp;Haide Qin,&nbsp;Honglian Ruan,&nbsp;Hao Huang,&nbsp;Tianxin Lin,&nbsp;Jian Huang","doi":"10.1002/cti2.1505","DOIUrl":"https://doi.org/10.1002/cti2.1505","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Lymphatic metastasis, an early stage of the metastasis process, is associated with adverse clinical outcomes in urothelial carcinoma of the bladder (UCB). However, the role of inflammation in triggering lymphatic metastasis remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We employed an RNA-sequencing cohort (<i>n</i> = 50) from Sun Yat-Sen Memorial Hospital (SYMH) to identify the most highly upregulated inflammatory gene associated with lymphatic metastasis. Using immunohistochemistry and immunofluorescence analyses, we validated the association of the identified molecule with clinical features and prognosis in an independent UCB cohort (<i>n</i> = 244) from SYMH. We also analysed TCGA-BLCA cohort (<i>n</i> = 408) to identify its potential biological pathways and immune landscape.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In our study, chitinase 3-like 1 (CHI3L1) emerged as a significantly overexpressed proinflammatory mediator in UCB tissues with lymphatic metastasis compared to those without lymphatic metastasis (81.1% vs. 47.8%, <i>P</i> &lt; 0.001). Within UCB tissues, CHI3L1 was expressed in both stromal cells (52.8%) and tumor cells (7.3%). Moreover, CHI3L1⁺ stromal cells, but not tumor cells, exhibited independent prognostic significance for both overall survival (<i>P</i> &lt; 0.001) and recurrence-free survival (<i>P</i> = 0.006). CHI3L1⁺ stromal cells were positively associated with D2-40⁺ lymphatic vessel density (<i>P</i> &lt; 0.001) and the immunosuppressive PD-L1/PD-1/CD8 axis in UCB tissues (all <i>P</i> &lt; 0.05). A bioinformatics analysis also identified a positive association between CHI3L1 expression and lymphangiogenesis or immunosuppression pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study established a clear association between stromal CHI3L1 expression and lymphatic metastasis, suggesting that stromal CHI3L1 expression is a potential prognostic marker for bladder cancer patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 4","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1505","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140553107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SARS-CoV-2-infected human airway epithelial cell cultures uniquely lack interferon and immediate early gene responses caused by other coronaviruses","authors":"Ying Wang,&nbsp;Melissa Thaler,&nbsp;Clarisse Salgado-Benvindo,&nbsp;Nathan Ly,&nbsp;Anouk A Leijs,&nbsp;Dennis K Ninaber,&nbsp;Philip M Hansbro,&nbsp;Fia Boedijono,&nbsp;Martijn J van Hemert,&nbsp;Pieter S Hiemstra,&nbsp;Anne M van der Does,&nbsp;Alen Faiz","doi":"10.1002/cti2.1503","DOIUrl":"https://doi.org/10.1002/cti2.1503","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a member of a class of highly pathogenic coronaviruses. The large family of coronaviruses, however, also includes members that cause only mild symptoms, like human coronavirus-229E (HCoV-229E) or OC43 (HCoV-OC43). Unravelling how molecular (and cellular) pathophysiology differs between highly and low pathogenic coronaviruses is important for the development of therapeutic strategies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Here, we analysed the transcriptome of primary human bronchial epithelial cells (PBEC), differentiated at the air–liquid interface (ALI) after infection with SARS-CoV-2, SARS-CoV, Middle East Respiratory Syndrome (MERS)-CoV and HCoV-229E using bulk RNA sequencing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>ALI-PBEC were efficiently infected by all viruses, and SARS-CoV, MERS-CoV and HCoV-229E infection resulted in a largely similar transcriptional response. The response to SARS-CoV-2 infection differed markedly as it uniquely lacked the increase in expression of immediate early genes, including <i>FOS</i>, <i>FOSB</i> and <i>NR4A1</i> that was observed with all other coronaviruses. This finding was further confirmed in publicly available experimental and clinical datasets. Interfering with NR4A1 signalling in Calu-3 lung epithelial cells resulted in a 100-fold reduction in extracellular RNA copies of SARS-CoV-2 and MERS-CoV, suggesting an involvement in virus replication. Furthermore, a lack in induction of interferon-related gene expression characterised the main difference between the highly pathogenic coronaviruses and low pathogenic viruses HCoV-229E and HCoV-OC43.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our results demonstrate a previously unknown suppression of a host response gene set by SARS-CoV-2 and confirm a difference in interferon-related gene expression between highly pathogenic and low pathogenic coronaviruses.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 4","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1503","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140553106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chimeric antigen receptor T cells in the fast lane among autoimmune disease therapies","authors":"Zhoujie Ding,&nbsp;David Tarlinton","doi":"10.1002/cti2.1502","DOIUrl":"https://doi.org/10.1002/cti2.1502","url":null,"abstract":"<p>In this commentary, we highlight recent studies demonstrating the feasibility and promise of chimeric antigen receptor (CAR) T-cell therapy in treating a number of autoimmune disorders including systemic lupus erythematosus and compare CAR T cells to other therapies aimed at depleting B-lineage cells in treating such diseases.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 4","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1502","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140546872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}