Clinical & Translational Immunology最新文献

{"title":"Spatial proteomic profiling of tumor and stromal compartments in non-small-cell lung cancer identifies signatures associated with overall survival","authors":"Vahid Yaghoubi Naei,&nbsp;James Monkman,&nbsp;Habib Sadeghirad,&nbsp;Ahmed Mehdi,&nbsp;Tony Blick,&nbsp;William Mullally,&nbsp;Ken O'Byrne,&nbsp;Majid Ebrahimi Warkiani,&nbsp;Arutha Kulasinghe","doi":"10.1002/cti2.1522","DOIUrl":"10.1002/cti2.1522","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Non-small-cell lung carcinoma (NSCLC) is the most prevalent and lethal form of lung cancer. The need for biomarker-informed stratification of targeted therapies has underpinned the need to uncover the underlying properties of the tumor microenvironment (TME) through high-plex quantitative assays.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, we profiled resected NSCLC tissues from 102 patients by targeted spatial proteomics of 78 proteins across tumor, immune activation, immune cell typing, immune-oncology, drug targets, cell death and PI3K/AKT modules to identify the tumor and stromal signatures associated with overall survival (OS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Survival analysis revealed that stromal CD56 (HR = 0.384, <i>P</i> = 0.06) and tumoral TIM3 (HR = 0.703, <i>P</i> = 0.05) were associated with better survival in univariate Cox models. In contrast, after adjusting for stage, BCLXL (HR = 2.093, <i>P</i> = 0.02) and cleaved caspase 9 (HR = 1.575, <i>P</i> = 0.1) negatively influenced survival. Delta testing indicated the protective effect of TIM-3 (HR = 0.614, <i>P</i> = 0.04) on OS. In multivariate analysis, CD56 (HR = 0.172, <i>P</i> = 0.001) was associated with better survival in the stroma, while B7.H3 (HR = 1.72, <i>P</i> = 0.008) was linked to poorer survival in the tumor.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Deciphering the TME using high-plex spatially resolved methods is giving us new insights into compartmentalised tumor and stromal protein signatures associated with clinical endpoints in NSCLC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 7","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11257771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141722755","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":"Endogenous bystander killing mechanisms enhance the activity of novel FAP-specific CAR-T cells against glioblastoma","authors":"Wenbo Yu,&nbsp;Nga TH Truong,&nbsp;Ruhi Polara,&nbsp;Tessa Gargett,&nbsp;Melinda N Tea,&nbsp;Stuart M Pitson,&nbsp;Michaelia P Cockshell,&nbsp;Claudine S Bonder,&nbsp;Lisa M Ebert,&nbsp;Michael P Brown","doi":"10.1002/cti2.1519","DOIUrl":"https://doi.org/10.1002/cti2.1519","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>CAR-T cells are being investigated as a novel immunotherapy for glioblastoma, but clinical success has been limited. We recently described fibroblast activation protein (FAP) as an ideal target antigen for glioblastoma immunotherapy, with expression on both tumor cells and tumor blood vessels. However, CAR-T cells targeting FAP have never been investigated as a therapy for glioblastoma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We generated a novel FAP targeting CAR with CD3ζ and CD28 signalling domains and tested the resulting CAR-T cells for their lytic activity and cytokine secretion function <i>in vitro</i> (using real-time impedance, flow cytometry, imaging and bead-based cytokine assays), and <i>in vivo</i> (using a xenograft mimicking the natural heterogeneity of human glioblastoma).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>FAP-CAR-T cells exhibited target specificity against model cell lines and potent cytotoxicity against patient-derived glioma neural stem cells, even when only a subpopulation expressed FAP, indicating a bystander killing mechanism. Using co-culture assays, we confirmed FAP-CAR-T cells mediate bystander killing of antigen-negative tumor cells, but only after activation by FAP-positive target cells. This bystander killing was at least partially mediated by soluble factors and amplified by IL-2 which activated the non-transduced fraction of the CAR-T product. Finally, a low dose of intravenously administered FAP-CAR-T cells controlled, without overt toxicity, the growth of subcutaneous tumors created using a mixture of antigen-negative and antigen-positive glioblastoma cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings advance FAP as a leading candidate for clinical CAR-T therapy of glioblastoma and highlight under-recognised antigen nonspecific mechanisms that may contribute meaningfully to the antitumor activity of CAR-T cells.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 7","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1519","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141537018","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":"Metabolic requirements of CD160 expressing memory-like NK cells in Gram-negative bacterial infection","authors":"Anucha Preechanukul,&nbsp;Natnaree Saiprom,&nbsp;Kitilak Rochaikun,&nbsp;Boonthanom Moonmueangsan,&nbsp;Rungnapa Phunpang,&nbsp;Orawan Ottiwet,&nbsp;Yuphin Kongphrai,&nbsp;Soonthon Wapee,&nbsp;Rachan Janon,&nbsp;Susanna Dunachie,&nbsp;Barbara Kronsteiner,&nbsp;Narisara Chantratita","doi":"10.1002/cti2.1513","DOIUrl":"10.1002/cti2.1513","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Unique metabolic requirements accompany the development and functional fates of immune cells. How cellular metabolism is important in natural killer (NK) cells and their memory-like differentiation in bacterial infections remains elusive.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Here, we utilise our established NK cell memory assay to investigate the metabolic requirement for memory-like NK cell formation and function in response to the Gram-negative intracellular bacteria <i>Burkholderia pseudomallei</i> (BP), the causative agent of melioidosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We demonstrate that CD160⁺ memory-like NK cells upon BP stimulation upregulate glucose and amino acid transporters in a cohort of recovered melioidosis patients which is maintained at least 3-month post-hospital admission. Using an <i>in vitro</i> assay, human BP-specific CD160⁺ memory-like NK cells show metabolic priming including increased expression of glucose and amino acid transporters with elevated glucose uptake, increased mTOR activation and mitochondrial membrane potential upon BP re-stimulation. Antigen-specific and cytokine-induced IFN-γ production of this memory-like NK cell subset are highly dependent on oxidative phosphorylation (OXPHOS) with some dependency on glycolysis, whereas the formation of CD160⁺ memory-like NK cells <i>in vitro</i> is dependent on fatty acid oxidation and OXPHOS and further increased by metformin.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study reveals the link between metabolism and cellular function of memory-like NK cells, which can be exploited for vaccine design and for monitoring protection against Gram-negative bacterial infection.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 7","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11218174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141490219","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":"Advances in bacteria-based drug delivery systems for anti-tumor therapy","authors":"Han Shuwen,&nbsp;Song Yifei,&nbsp;Wu Xinyue,&nbsp;Qu Zhanbo,&nbsp;Yu Xiang,&nbsp;Yang Xi","doi":"10.1002/cti2.1518","DOIUrl":"10.1002/cti2.1518","url":null,"abstract":"<p>In recent years, bacteria have gained considerable attention as a promising drug carrier that is critical in improving the effectiveness and reducing the side effects of anti-tumor drugs. Drug carriers can be utilised in various forms, including magnetotactic bacteria, bacterial biohybrids, minicells, bacterial ghosts and bacterial spores. Additionally, functionalised and engineered bacteria obtained through gene engineering and surface modification could provide enhanced capabilities for drug delivery. This review summarises the current studies on bacteria-based drug delivery systems for anti-tumor therapy and discusses the prospects and challenges of bacteria as drug carriers. Furthermore, our findings aim to provide new directions and guidance for the research on bacteria-based drug systems.</p>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 7","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11208082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141464616","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":"Siglec-1, an easy and contributory inflammation marker in rheumatology","authors":"Valentina Boz,&nbsp;Alessandra Tesser,&nbsp;Francesca Burlo,&nbsp;Nicola Donadel,&nbsp;Serena Pastore,&nbsp;Alessandro Amaddeo,&nbsp;Francesca Vittoria,&nbsp;Matteo Padovan,&nbsp;Marianna Di Rosa,&nbsp;Alberto Tommasini,&nbsp;Erica Valencic","doi":"10.1002/cti2.1520","DOIUrl":"10.1002/cti2.1520","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Inflammatory markers such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are poorly informative about interferon (IFN)-related disorders. In these conditions, the measure of the interferon score (IS), obtained by measuring the expression of IFN-stimulated genes, has been proposed. Flow cytometry-based assays measuring sialic-acid-binding Ig-like lectin 1 (Siglec-1) expression could be a more practical tool for evaluating IFN-inflammation. The study compared Siglec-1 measures with IS and other inflammatory indexes. We compared Siglec-1 measures with IS and other inflammatory indexes in real-world paediatric rheumatology experience.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We recruited patients with immuno-rheumatological conditions, acute infectious illness and patients undergoing orthopaedic surgery as controls. Siglec-1 expression was measured in all samples, and IS, ESR and CRP were also recorded if available.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Overall, 98 subjects were enrolled in the study, with a total of 104 measures of Siglec-1. Compared with IS, Siglec-1 expression showed good accuracy (86.0%), specificity (72.7%) and sensitivity (85.7%). The measure of the percentage of Siglec-1-positive cells performed best at low levels of IFN-inflammation, while the measure of mean fluorescence intensity performed best at higher levels. <i>Ex vivo</i> studies on IFN-stimulated monocytes confirmed this behaviour. There was no link between Siglec-1 expression and either ESR or CRP, and positive Siglec-1 results were found even when ESR and CRP were normal. A high Siglec-1 expression was also recorded in subjects with acute infections.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Siglec-1 measurement by flow cytometry is an easy tool to detect IFN-related inflammation, even in subjects with normal results of common inflammation indexes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 7","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11208081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141464617","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":"Serum AZD7442 (tixagevimab–cilgavimab) concentrations and in vitro IC50 values predict SARS-CoV-2 neutralising antibody titres","authors":"Lindsay E Clegg,&nbsp;Oleg Stepanov,&nbsp;Sam Matthews,&nbsp;Tom White,&nbsp;Seth Seegobin,&nbsp;Steven Thomas,&nbsp;Kevin M Tuffy,&nbsp;Mats Någård,&nbsp;Mark T Esser,&nbsp;Katie Streicher,&nbsp;Taylor S Cohen,&nbsp;Anastasia A Aksyuk","doi":"10.1002/cti2.1517","DOIUrl":"10.1002/cti2.1517","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) necessitates rapid methods for assessing monoclonal antibody (mAb) potency against emerging variants. Authentic virus neutralisation assays are considered the gold standard for measuring virus-neutralising antibody (nAb) titres in serum. However, authentic virus-based assays pose inherent practical challenges for measuring nAb titres against emerging SARS-CoV-2 variants (e.g. storing infectious viruses and testing at biosafety level-3 facilities). Here, we demonstrate the utility of pseudovirus neutralisation assay data in conjunction with serum mAb concentrations to robustly predict nAb titres in serum.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>SARS-CoV-2 nAb titres were determined via authentic- and lentiviral pseudovirus-based neutralisation assays using serological data from three AZD7442 (tixagevimab–cilgavimab) studies: PROVENT (NCT04625725), TACKLE (NCT04723394) and a phase 1 dose-ranging study (NCT04507256). AZD7442 serum concentrations were assessed using immunocapture. Serum-based half-maximal inhibitory concentration (IC₅₀) values were derived from pseudovirus nAb titres and serum mAb concentrations, and compared with <i>in vitro</i> IC₅₀ measurements.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>nAb titres measured via authentic- and lentiviral pseudovirus-based neutralisation assays were strongly correlated for the ancestral SARS-CoV-2 virus and SARS-CoV-2 Alpha. Serum AZD7442 concentrations and pseudovirus nAb titres were strongly correlated for multiple SARS-CoV-2 variants with all Spearman correlation coefficients ≥ 0.78. Serum-based IC₅₀ values were similar to <i>in vitro</i> IC₅₀ values for AZD7442, for ancestral SARS-CoV-2 and Alpha, Delta, Omicron BA.2 and Omicron BA.4/5 variants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These data highlight that serum mAb concentrations and pseudovirus <i>in vitro</i> IC₅₀ values can be used to rapidly predict nAb titres in serum for emerging and historical SARS-CoV-2 variants.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 6","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11175839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141316242","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":"Dupilumab improves outcomes in patients with chronic rhinosinusitis with nasal polyps irrespective of gender: results from the SINUS-52 trial","authors":"Wytske J Fokkens,&nbsp;Claus Bachert,&nbsp;Claire Hopkins,&nbsp;Osama Marglani,&nbsp;Amy Praestgaard,&nbsp;Scott Nash,&nbsp;Yamo Deniz,&nbsp;Paul J Rowe,&nbsp;Harry Sacks,&nbsp;Juby A Jacob-Nara","doi":"10.1002/cti2.1511","DOIUrl":"https://doi.org/10.1002/cti2.1511","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>This <i>post hoc</i> analysis assessed disease characteristics and response to dupilumab treatment in male and female patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) (SINUS-52 study; NCT02898454).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients received dupilumab 300 mg or placebo every 2 weeks for 52 weeks on background intranasal corticosteroids. Efficacy was assessed through Week 52 using nasal polyp score (NPS), nasal congestion/obstruction score, loss of smell score and University of Pennsylvania Smell Identification Test score. Disease-specific health-related quality of life (HRQoL) was assessed using the 22-item Sino-Nasal Outcome Test (SNOT-22).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The analysis included 192 male and 111 female patients. Female patients had higher mean SNOT-22 total score (56.6 vs. 49.1, <i>P</i> &lt; 0.01) and more coexisting asthma (78.4% vs. 46.4%, <i>P</i> &lt; 0.0001) and non-steroidal anti-inflammatory drug-exacerbated respiratory disease (NSAID-ERD) (38.7% vs. 18.8%, <i>P</i> = 0.0001) than male patients, but other baseline characteristics were similar. Dupilumab significantly improved CRSwNP outcomes vs. placebo at Week 52, regardless of gender: least squares mean differences (95% confidence interval) for NPS were −2.33 (−2.80, −1.86) in male and −2.54 (−3.18, −1.90) in female patients (both <i>P</i> &lt; 0.0001 vs. placebo), and for SNOT-22 were −19.2 (−24.1, −14.2) in male and −24.4 (−31.5, −17.3) in female patients (both <i>P</i> &lt; 0.0001 vs. placebo). There were no significant efficacy-by-gender interactions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Female patients had greater asthma, NSAID-ERD and HRQoL burden at baseline than male patients. Dupilumab treatment significantly improved objective and subjective outcomes compared with placebo, irrespective of gender.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 6","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1511","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141292571","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 circulating tumor-associated and immune cells in patients with advanced-stage non-small cell lung cancer","authors":"Vahid Yaghoubi Naei,&nbsp;Ekaterina Ivanova,&nbsp;William Mullally,&nbsp;Connor G O'Leary,&nbsp;Rahul Ladwa,&nbsp;Ken O'Byrne,&nbsp;Majid E Warkiani,&nbsp;Arutha Kulasinghe","doi":"10.1002/cti2.1516","DOIUrl":"https://doi.org/10.1002/cti2.1516","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Globally, non-small cell lung cancer (NSCLC) is the most prevalent form of lung cancer and the leading cause of cancer-related deaths. Tumor-associated circulating cells in NSCLC can have a wide variety of morphological and phenotypic characteristics, including epithelial, immunological or hybrid subtypes. The distinctive characteristics and potential clinical significance of these cells in patients with NSCLC are explored in this study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We utilised a spiral microfluidic device to enrich large cells and cell aggregates from the peripheral blood samples of NSCLC patients. These cells were characterised through high-resolution immunofluorescent imaging and statistical analysis, correlating findings with clinical information from our patient cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We have identified varied populations of heterotypic circulating tumor cell clusters with differing immune cell composition that included a distinct class of atypical tumor-associated macrophages that exhibits unique morphology and cell size. This subtype's prevalence is positively correlated with the tumor stage, progression and metastasis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our study reveals a heterogeneous landscape of circulating tumor cells and their clusters, underscoring the complexity of NSCLC pathobiology. The identification of a unique subtype of atypical tumor-associatedmacrophages that simultaneously express both tumor and immune markers and whose presence correlates with late disease stages, poor clinical outcomes and metastatic risk infers  the potential of these cells as biomarkers for NSCLC staging and prognosis. Future studies should focus on the role of these cells in the tumor microenvironment and their potential as therapeutic targets. Additionally, longitudinal studies tracking these cell types through disease progression could provide further insights into their roles in NSCLC evolution and response to treatment.</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/cti2.1516","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141245980","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":"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}