Clinical & Translational Immunology最新文献

{"title":"Dual CD47 and PD-L1 blockade elicits anti-tumor immunity by intratumoral CD8+ T cells","authors":"Susan N Christo,&nbsp;Keely M McDonald,&nbsp;Thomas N Burn,&nbsp;Nadia Kurd,&nbsp;Jessica Stanfield,&nbsp;Megan M Kaneda,&nbsp;Ruth Seelige,&nbsp;Christopher P Dillon,&nbsp;Timothy S Fisher,&nbsp;Bas Baaten,&nbsp;Laura K Mackay","doi":"10.1002/cti2.70014","DOIUrl":"https://doi.org/10.1002/cti2.70014","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Bispecific antibodies targeting CD47 and PD-L1 (CD47 × PD-L1 BisAb) demonstrate efficacy against a range of solid cancers. While dual blockade negates anti-CD47-mediated toxicity, the effect of combined innate and adaptive immune activation on protective tumor-resident CD8⁺ T cells has yet to be fully elucidated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>CD8⁺ T cell populations were tracked upon CD47 × PD-L1 BisAb treatment in an orthotopic model of murine breast cancer where anti-tumor immunity is mediated by CD8⁺ T cells. Immune responses were also compared with anti-PD-L1 monotherapy to assess the advantage of dual checkpoint targeting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that CD47 × PD-L1 BisAb treatment augmented CD8⁺ T cell responses in tumors, which resulted in enhanced tumor control. Compared with anti-PD-L1 treatment, dual CD47 and PD-L1 blockade promoted greater numbers of antigen-specific tumor-resident CD8⁺ T cells that exhibited increased cytokine production.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Engagement of innate and adaptive immune checkpoint molecules via CD47 × PD-L1 BisAb treatment resulted in robust CD8⁺ T cell responses, including the induction of tumor-resident CD8⁺ T cells that exhibited functionally superior anti-tumor immunity. These results demonstrate that innate immune activation potentiates anti-tumor adaptive responses, highlighting the use of dual checkpoint blockade as an optimal strategy for promoting CD8⁺ T cell-mediated protection.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 11","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142707678","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":"Autologous Epstein–Barr virus-specific adoptive T-cell therapy in a patient with lupus nephritis","authors":"Dwarakanathan Ranganathan,&nbsp;Saskia Leibowitz,&nbsp;George T John,&nbsp;Michelle A Neller,&nbsp;George R Ambalathingal,&nbsp;Leone Beagley,&nbsp;Archana Panikkar,&nbsp;Shannon Best,&nbsp;Jyothy Raju,&nbsp;Hilary Reddiex,&nbsp;Sharad Ratanjee,&nbsp;Monica Suet Ying Ng,&nbsp;Corey Smith,&nbsp;Rajiv Khanna","doi":"10.1002/cti2.70015","DOIUrl":"10.1002/cti2.70015","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Dysregulation of Epstein–Barr virus (EBV)-specific cellular immunity has been hypothesised as one of the contributing factors in the pathogenesis of systemic lupus erythematosus (SLE). Lupus nephritis is a major risk factor for overall morbidity in SLE. Immune-based strategies directed to EBV have been proposed as potential therapeutic strategy for SLE and lupus nephritis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Autologous EBV latent antigen-specific CD4⁺ and CD8⁺ T cells were expanded <i>in vitro</i> and adoptively transferred to a lupus nephritis patient.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This adoptive immunotherapy had no immediate adverse effects, and the patient was subsequently treated with the anti-CD20 antibody, obinutuzumab. The patient showed a reduction in anti-dsDNA antibodies and improved glomerular filtration rate but remained nephrotic. These observations were coincident with a reduction in anti-viral and global T-cell activation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>To our knowledge, this is the first report of the use of EBV-specific adoptive immunotherapy to treat a patient with lupus nephritis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 11","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11574558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674667","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":"The contribution of the CRP/CD64 axis to renal cancer progression by inducing protumor activation of tumor-associated macrophages","authors":"Cheng Pan,&nbsp;Yukio Fujiwara,&nbsp;Hiromu Yano,&nbsp;Toshiki Anami,&nbsp;Yuki Ibe,&nbsp;Lianbo Li,&nbsp;Yuji Miura,&nbsp;Takanobu Motoshima,&nbsp;Shigeyuki Esumi,&nbsp;Junji Yatsuda,&nbsp;Taizo Hibi,&nbsp;Tomomi Kamba,&nbsp;Yoshihiro Komohara","doi":"10.1002/cti2.70013","DOIUrl":"10.1002/cti2.70013","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>C-reactive protein (CRP) is a well-known acute-phase protein that increases remarkably under various inflammatory conditions and is elevated in patients with malignant tumors. In this study, we investigated the influence of CRP on the tumor microenvironment in clear cell renal cell carcinoma (ccRCC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study explored CRP's role in ccRCC by co-culturing human macrophages with ccRCC cells and employing antibody blocking, RNA sequencing and <i>in vitro</i> experiments for functional insights. We also analysed The Cancer Genome Atlas Program (TCGA) data to link CD64 expression with ccRCC prognosis and used immunohistochemistry to associate CD64⁺ macrophages with tumor severity and systemic CRP levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A co-culture study using human macrophages and RCC cell lines showed that CRP-stimulated macrophages secrete IL-6, which induces RCC proliferation via STAT3 activation. CRP-induced protumor activation of macrophages was suppressed by CD64 blocking antibodies. Furthermore, CRP elevates PD-L1 expression in macrophages via the CD64-STAT1 signalling pathway. Statistical analysis of TCGA data indicated that increased CD64 expression was associated with a worse clinical course in ccRCC. Immunohistochemical analysis of pathological specimens revealed that high CD64 expression in tumor-associated macrophages (TAMs), and a high density of CD64⁺ TAMs, was linked to high nuclear grade and stage. High CD64 expression was also correlated with increased serum CRP levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The CRP-CD64 signal was linked to the protumor activation of TAMs and could be a promising target for anticancer immunotherapy in ccRCC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 11","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11574560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674669","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":"Natural killer cell antibody-dependent cellular cytotoxicity to Plasmodium falciparum is impacted by cellular phenotypes, erythrocyte polymorphisms, parasite diversity and intensity of transmission","authors":"Stephen Tukwasibwe,&nbsp;Savannah Nicole Lewis,&nbsp;Yoweri Taremwa,&nbsp;Kattria van der Ploeg,&nbsp;Kathleen D Press,&nbsp;Maureen Ty,&nbsp;Felistas Namirimu Nankya,&nbsp;Kenneth Musinguzi,&nbsp;Evelyn Nansubuga,&nbsp;Florian Bach,&nbsp;Martin Chamai,&nbsp;Martin Okitwi,&nbsp;Gerald Tumusiime,&nbsp;Annettee Nakimuli,&nbsp;Francesco Colucci,&nbsp;Moses R Kamya,&nbsp;Joaniter I Nankabirwa,&nbsp;Emmanuel Arinaitwe,&nbsp;Bryan Greenhouse,&nbsp;Grant Dorsey,&nbsp;Philip J Rosenthal,&nbsp;Isaac Ssewanyana,&nbsp;Prasanna Jagannathan","doi":"10.1002/cti2.70005","DOIUrl":"https://doi.org/10.1002/cti2.70005","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Natural killer (NK) cells make important contributions to anti-malarial immunity through antibody-dependent cellular cytotoxicity (ADCC), but the role of different components of this pathway in promoting NK cell activation remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We compared the functions and phenotypes of NK cells from malaria-exposed and malaria-naive donors, and then varied the erythrocyte genetic background, <i>Plasmodium falciparum</i> strain and opsonising plasma used in ADCC to observe their impacts on NK cell degranulation as measured by CD107a mobilisation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Natural killer cells from malaria-exposed adult Ugandan donors had enhanced ADCC, but an impaired pro-inflammatory response to cytokine stimulation, compared to NK cells obtained from malaria-naive adult North American donors. Cellular phenotypes from malaria-exposed donors reflected this specialisation for ADCC, with a compartment-wide downregulation of the Fc receptor γ-chain and enrichment of highly differentiated CD56^dim and CD56^neg populations. NK cell degranulation was enhanced in response to opsonised <i>P. falciparum</i> schizonts cultured in sickle cell heterozygous erythrocytes relative to wild-type erythrocytes, and when using opsonising plasma collected from donors living in a high transmission area compared to a lower transmission area despite similar levels of 3D7 schizont-specific IgG levels. However, degranulation was lowered in response to opsonised field isolate <i>P. falciparum</i> schizonts isolated from clinical malaria infections, compared to the 3D7 laboratory strain typically used in these assays.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This work highlights important host and parasite factors that contribute to ADCC efficacy that should be considered in the design of ADCC assays.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 11","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142561635","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":"Naturally acquired adaptive immunity to Streptococcus pneumoniae is impaired in rheumatoid arthritis patients","authors":"Giuseppe Ercoli,&nbsp;Hugh Selway-Clarke,&nbsp;Dena Truijen,&nbsp;Milda Folkmanaite,&nbsp;Tate Oulton,&nbsp;Caitlin Norris-Grey,&nbsp;Rie Nakajima,&nbsp;Philip Felgner,&nbsp;Brendan W Wren,&nbsp;Kevin Tetteh,&nbsp;Nicholas J Croucher,&nbsp;Maria Leandro,&nbsp;Geraldine Cambridge,&nbsp;Jeremy S Brown","doi":"10.1002/cti2.70012","DOIUrl":"https://doi.org/10.1002/cti2.70012","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Patients with rheumatoid arthritis (RA) have an increased susceptibility to infections, including those caused by <i>Streptococcus pneumoniae</i>. Why RA is associated with increased susceptibility to <i>S. pneumoniae</i> is poorly understood. This study aims to assess the effects of RA and B-cell depletion therapy on naturally acquired antibody responses to 289 <i>S. pneumoniae</i> protein antigens using a novel protein array.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>IgG responses to <i>S. pneumoniae</i> were characterised in serum from RA patients and disease controls (myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)) using whole-cell ELISA, a flow cytometry opsonisation assay and an <i>S. pneumoniae</i> protein array. For the RA patients, results were compared before and after B-cell depletion therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared to a well-characterised disease control group of ME/CFS patients, RA patients had reduced antibody responses to multiple <i>S. pneumoniae</i> protein antigens, with significant IgG recognition of approximately half the number of antigens along with reduced median strengths of these responses. Reduction in multiple array antigen-specific responses also correlated with reduced IgG opsonisation of <i>S. pneumoniae</i>. Although B-cell depletion therapy with rituximab did not reduce overall IgG recognition of <i>S. pneumoniae</i> in the RA group, it was associated with marked disruption of pre-existing IgG repertoire to protein antigens in individual patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These data show RA is associated with major disruption of naturally acquired adaptive immunity to <i>S. pneumoniae</i>, which can be assessed rapidly using a protein antigen array and is likely to contribute towards the increased incidence of pneumonia in patients with RA.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 10","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443415","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":"Inhibitory effect of hydroxychloroquine on glucocorticoid-induced osteoporosis in lupus therapy","authors":"Wenlin Qiu,&nbsp;Xiaoxiao Han,&nbsp;Tong Yu,&nbsp;Lijuan Jiang,&nbsp;Xuefei Wang,&nbsp;Ruizhi Feng,&nbsp;Xiaoru Duan,&nbsp;Yao Teng,&nbsp;Haifeng Yin,&nbsp;Maria I Bokarewa,&nbsp;Guo-Min Deng","doi":"10.1002/cti2.70010","DOIUrl":"https://doi.org/10.1002/cti2.70010","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Systemic lupus erythematosus (SLE) is a chronic and severe autoimmune disease characterised by persistent inflammation. Hydroxychloroquine (HCQ) and glucocorticoids (GCs) are the primary agents commonly used in combination as the first-line treatment for SLE. Nevertheless, the specific mechanisms responsible for the effectiveness of this combined therapy with HCQ and GCs have not been fully elucidated. This study aimed to reveal the mechanism behind combined HCQ and GC treatment in lupus.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>An SLE IgG-induced inflammation model was used to investigate the anti-inflammatory effects of HCQ and dexamethasone (DXM). A glucocorticoid-induced osteoporosis (GIOP) model was used to investigate the inhibitory effect of HCQ on osteoclastogenesis. Inflammation was assessed by haematoxylin and eosin staining. Bone metabolism was determined structurally via microcomputer tomography and in bone marrow-derived osteoclast cultures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>An SLE IgG-induced inflammation model demonstrated that HCQ could not ameliorate inflammation alone but could enhance the anti-inflammatory effect of GCs by decreasing the expression of FcγRI on macrophages. HCQ inhibited osteoclastogenesis induced by GCs and RANKL by upregulating nuclear factor erythroid 2-related factor 2 and limiting reactive oxygen species formation, which mitigated GC-induced bone loss.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The results indicate that HCQ improved the anti-inflammatory effects of GCs and inhibits the osteoclastogenesis in experimental lupus. This study offers valuable insights into the mechanisms underlying the combined treatment of lupus with HCQ and GCs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 10","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435410","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":"Lymphocyte activation gene 3 served as a potential prognostic and immunological biomarker across various cancer types: a clinical and pan-cancer analysis","authors":"Yifan Liu,&nbsp;Yuntao Yao,&nbsp;Xinyue Yang,&nbsp;Maodong Wei,&nbsp;Bingnan Lu,&nbsp;Keqing Dong,&nbsp;Donghao Lyu,&nbsp;Yuanan Li,&nbsp;Wenbin Guan,&nbsp;Runzhi Huang,&nbsp;Guofeng Xu,&nbsp;Xiuwu Pan","doi":"10.1002/cti2.70009","DOIUrl":"10.1002/cti2.70009","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Lymphocyte activation gene 3 (LAG3), an inhibitory receptor in T-cell activation, is a negative prognostic factor. However, its impact on tumours has yet to be comprehensively elucidated on a pan-cancer scale. Thus, we aim to reveal its role at the pan-cancer level.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed IHC staining on a retrospective cohort of 370 patients. Then we assessed the prognostic effect of LAG3 using Kaplan–Meier survival analysis and multivariate Cox regression analysis. In pan-cancer analysis, we constructed competing endogenous RNA and protein–protein interaction networks, conducted gene set enrichment analysis and identified correlations between LAG3 gene expression and various factors, including clinical characteristics, tumour purity, mutations, tumour immunity and drug sensitivity across 33 cancer types.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>LAG3 was expressed higher in normal kidney tissues than in tumours. A high level of LAG3 gene expression was an independent prognostic factor for OS (HR = 6.60, 95% CI = 2.43–17.90, <i>P</i> &lt; 0.001) and PFS (HR = 3.44, 95% CI = 1.68–7.10, <i>P</i> &lt; 0.001). In pan-cancer analysis, LAG3 exhibited robust correlations with survival and tumour stages in various cancers. Moreover, LAG3 was strongly associated with immune-related genes, proteins and signalling pathways. LAG3 gene expression was positively associated with increased infiltration of activated immune cells and decreased infiltration of several resting cells. LAG3 gene expression was associated with tumour mutation burden and microsatellite instability in multiple cancers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>High LAG3 gene expression was an independent risk factor in kidney neoplasms. It also functioned as a biomarker for prognosis, TIME and immunotherapy efficacy in the pan-cancer dimension.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 10","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11450455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379659","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":"Targeting CD38 with monoclonal antibodies disrupts key survival pathways in paediatric Burkitt's lymphoma malignant B cells","authors":"Kathrin Kläsener,&nbsp;Nadja Herrmann,&nbsp;Liliana Håversen,&nbsp;Timothy Sundell,&nbsp;Martina Sundqvist,&nbsp;Christina Lundqvist,&nbsp;Paul T Manna,&nbsp;Charlotte A Jonsson,&nbsp;Marcella Visentini,&nbsp;Diana Ljung Sass,&nbsp;Sarah McGrath,&nbsp;Kristoffer Grimstad,&nbsp;Alaitz Aranburu,&nbsp;Karin Mellgren,&nbsp;Linda Fogelstrand,&nbsp;Huamei Forsman,&nbsp;Olov Ekwall,&nbsp;Jan Borén,&nbsp;Inger Gjertsson,&nbsp;Michael Reth,&nbsp;Inga-Lill Mårtensson,&nbsp;Alessandro Camponeschi","doi":"10.1002/cti2.70011","DOIUrl":"10.1002/cti2.70011","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Paediatric Burkitt's lymphoma (pBL) is the most common childhood non-Hodgkin B-cell lymphoma. Despite the encouraging survival rates for most children, treating cases with relapse/resistance to current therapies remains challenging. CD38 is a transmembrane protein highly expressed in pBL. This study investigates the effectiveness of CD38-targeting monoclonal antibodies (mAbs), daratumumab and isatuximab, in impairing crucial cellular processes and survival pathways in pBL malignant cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p><i>In silico</i> analyses of patient samples, combined with <i>in vitro</i> experiments using the Ramos cell line, were conducted to assess the impact of daratumumab and isatuximab on cellular proliferation, apoptosis and the phosphoinositide 3-kinase (PI3K) pathway.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Isatuximab was found to be more effective than daratumumab in disrupting B-cell receptor signalling, reducing cellular proliferation and inducing apoptosis. Additionally, isatuximab caused a significant impairment of the PI3K pathway and induced metabolic reprogramming in pBL cells. The study also revealed a correlation between CD38 and MYC expression levels in pBL patient samples, suggesting CD38 involvement in key oncogenic processes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The study emphasises the therapeutic potential of CD38-targeting mAbs, particularly isatuximab, in pBL.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 10","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370396","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":"Humoral and cellular immune responses in vaccinated and unvaccinated children following SARS-CoV-2 Omicron infection","authors":"Zheng Quan Toh,&nbsp;Jeremy Anderson,&nbsp;Nadia Mazarakis,&nbsp;Leanne Quah,&nbsp;Jill Nguyen,&nbsp;Rachel A Higgins,&nbsp;Lien Anh Ha Do,&nbsp;Yan Yung Ng,&nbsp;Sedi Jalali,&nbsp;Melanie R Neeland,&nbsp;Alissa McMinn,&nbsp;Richard Saffery,&nbsp;Sarah McNab,&nbsp;Jodie McVernon,&nbsp;Adrian Marcato,&nbsp;David P Burgner,&nbsp;Nigel Curtis,&nbsp;Andrew C Steer,&nbsp;Kim Mulholland,&nbsp;Daniel G Pellicci,&nbsp;Nigel W Crawford,&nbsp;Shidan Tosif,&nbsp;Paul V Licciardi","doi":"10.1002/cti2.70008","DOIUrl":"10.1002/cti2.70008","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>The immune response in children elicited by SARS-CoV-2 Omicron infection alone or in combination with COVID-19 vaccination (hybrid immunity) is poorly understood. We examined the humoral and cellular immune response following SARS-CoV-2 Omicron infection in unvaccinated children and children who were previously vaccinated with COVID-19 mRNA vaccine.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Participants were recruited as part of a household cohort study conducted during the Omicron predominant wave (Jan to July 2022) in Victoria, Australia. Blood samples were collected at 1, 3, 6 and 12 months following COVID-19 diagnosis. Humoral immune responses to SARS-CoV-2 Spike proteins from Wuhan, Omicron BA.1, BA.4/5 and JN.1, as well as cellular immune responses to Wuhan and BA.1 were assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 43 children and 113 samples were included in the analysis. Following Omicron infection, unvaccinated children generated low antibody responses but elicited Spike-specific CD4 and CD8 T-cell responses. In contrast, vaccinated children infected with the Omicron variant mounted robust humoral and cellular immune responses to both ancestral strain and Omicron subvariants. Hybrid immunity persisted for at least 6 months post infection, with cellular immune memory characterised by the generation of Spike-specific polyfunctional CD8 T-cell responses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>SARS-CoV-2 hybrid immunity in children is characterised by persisting SARS-CoV-2 antibodies and robust CD4 and CD8 T-cell activation and polyfunctional responses. Our findings contribute to understanding hybrid immunity in children and may have implications regarding COVID-19 vaccination and SARS-CoV-2 re-infections.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 10","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370395","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":"IL-15-induced CD38+HLA-DR+CD8+ T cells correlate with liver injury via NKG2D in chronic hepatitis B cirrhosis","authors":"Jing Fan,&nbsp;Min Xu,&nbsp;Ke Liu,&nbsp;Wanping Yan,&nbsp;Huanyu Wu,&nbsp;Hongliang Dong,&nbsp;Yongfeng Yang,&nbsp;Wei Ye","doi":"10.1002/cti2.70007","DOIUrl":"https://doi.org/10.1002/cti2.70007","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>CD8⁺ T cells play a critical role in the immune dysfunction associated with liver cirrhosis. CD38⁺HLA-DR⁺CD8⁺ T cells, or bystander-activated CD8⁺ T cells, are involved in tissue injury but their specific contribution to liver cirrhosis remains unclear. This study sought to identify the mechanism for CD38⁺HLA-DR⁺CD8⁺ T cell-mediated pathogenesis during liver cirrhosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The immunophenotype, antigen specificity, cytokine secretion and cytotoxicity-related indicators of CD38⁺HLA-DR⁺CD8⁺ T cells were determined using flow cytometry. The functional properties of these cells were assessed using transcriptome analysis. CD38⁺HLA-DR⁺CD8⁺ T-cell killing was detected using cytotoxicity and antibody-blocking assays.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The proportion of CD38⁺HLA-DR⁺CD8⁺ T cells was significantly elevated in liver cirrhosis patients and correlated with tissue damage. Transcriptome analysis revealed that these cells had innate-like functional characteristics. This CD8⁺ T-cell population primarily consisted of effector memory T cells and produced a high level of cytotoxicity-related cytokines, granzyme B and perforin. IL-15 promoted CD38⁺HLA-DR⁺CD8⁺ T-cell activation and proliferation, inducing significant TCR-independent cytotoxicity mediated through NKG2D.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>CD38⁺HLA-DR⁺CD8⁺ T cells correlated with cirrhosis-related liver injury and contributed to liver damage by signalling through NKG2D in a TCR-independent manner.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 10","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142404496","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}