Clinical & Translational Immunology最新文献

{"title":"Autoantibodies in hospitalised patients with COVID-19.","authors":"Eleni Tiniakou, Livia Casciola-Rosen, Mekha A Thomas, Yuka Manabe, Annukka Ar Antar, Mahendra Damarla, Paul M Hassoun, Li Gao, Zitong Wang, Scott Zeger, Antony Rosen","doi":"10.1002/cti2.70019","DOIUrl":"10.1002/cti2.70019","url":null,"abstract":"<p><strong>Objectives: </strong>CD209L and its homologous protein CD209 act as alternative entry receptors for the SARS-CoV-2 virus and are highly expressed in the virally targeted tissues. We tested for the presence and clinical features of autoantibodies targeting these receptors and compared these with autoantibodies known to be associated with COVID-19.</p><p><strong>Methods: </strong>Using banked samples (<i>n</i> = 118) from Johns Hopkins patients hospitalised with COVID-19, we defined autoantibodies against CD209 and CD209L by enzyme-linked immunosorbent assay (ELISA). Clinical associations of these antibodies were compared with those of patients with anti-interferon (IFN) and anti-angiotensin-converting enzyme-2 (ACE2) autoantibodies.</p><p><strong>Results: </strong>Amongst patients hospitalised with COVID-19, 19.5% (23/118) had IgM autoantibodies against CD209L and were more likely to have coronary artery disease (44% vs 19%, <i>P</i> = 0.03). Antibodies against CD209 were present in 5.9% (7/118); interestingly, all 7 were male (<i>P</i> = 0.02). In our study, the presence of either antibody was positively associated with disease severity [OR 95% confidence interval (95% CI): 1.80 (0.69-5.03)], but the association did not reach statistical significance. In contrast, 10/118 (8.5%) had IgG autoantibodies against IFNα, and 21 (17.8%) had IgM antibodies against ACE2. These patients had significantly worse prognosis (intubation or death) and prolonged hospital stays. However, when adjusting for patient characteristics on admission, only the presence of anti-ACE2 IgM remained significant [pooled common OR (95% CI), 4.14 (1.37, 12.54)].</p><p><strong>Conclusion: </strong>We describe IgM autoantibodies against CD209 and CD209L amongst patients hospitalised with COVID-19. These were not associated with disease severity. Conversely, patients with either anti-ACE2 IgM or anti-IFNα IgG antibodies had worse outcomes. Due to the small size of the study cohort, conclusions drawn should be considered cautiously.</p>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 12","pages":"e70019"},"PeriodicalIF":4.6,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11671454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142902525","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":"A preclinical study of allogeneic CD19 chimeric antigen receptor double-negative T cells as an off-the-shelf immunotherapy drug against B-cell malignancies.","authors":"Dan Wang, Liuyang Wang, Shuai Liu, Jianjun Tong, Honglin Zhu, Man Xu, Xiancai Li, Zhiqiang Xiang, Qinghua Sun, Hengcai Wang, Yuli Wang, Shuyang Wang, Liming Yang","doi":"10.1002/cti2.70022","DOIUrl":"10.1002/cti2.70022","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate the manufacturability, efficacy and safety of allogeneic CD19 chimeric antigen receptor double-negative T cells (CD19-CAR-DNTs) as an off-the-shelf therapeutic cell product.</p><p><strong>Methods: </strong>A membrane proteome array was used to assess the off-target binding of CD19-CAR. DNTs derived from healthy donors were transduced with lentiviral vectors encoding the CD19-CAR. The manufacture of the CD19-CAR-DNTs was under GMP conditions, and their surface molecule expression patterns were characterised using flow cytometry. We investigated the off-the-shelf potential of CD19-CAR-DNTs by evaluating the cryopreserved CD19-CAR-DNTs in terms of cell viability as well as their cytotoxicity against various CD19⁺ target cell lines and primary patient blasts <i>in vitro.</i> We evaluated the persistence and safety of the cryopreserved CD19-CAR-DNTs in xenograft models <i>in vivo</i>.</p><p><strong>Results: </strong>GMP-grade CD19-CAR-DNTs were manufactured and cryopreserved for use in advance. The cryopreserved CD19-CAR-DNTs maintain their viability and antitumor activity against various CD19⁺ target cell lines and primary patient blasts. These cells significantly prolonged the survival in Raji-Luc-xenografted NOG mice. Multiple infusions of the cells can further augment their efficacy. Remarkably, following a single infusion in mice, CD19-CAR-DNTs rapidly got distributed among well-perfused organs initially, and progressively spread to most tissues, peaking at Day 43. In toxicity studies, CD19-CAR-DNTs significantly reduced tumor burden and ameliorated tissue damage in tumor-bearing NOG mice. Critically, no immunotoxicity or graft versus host disease was observed in non-tumor-bearing NOG mice.</p><p><strong>Conclusions: </strong>The allogeneic CD19-CAR-DNTs fulfil the requirements of an off-the-shelf therapeutic cell product, offering a promising new approach to the treatment of haematological malignancies.</p>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 12","pages":"e70022"},"PeriodicalIF":4.6,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884898","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":"Improving diagnosis in patients with obstetric antiphospholipid syndrome through the evaluation of non-criteria antibodies","authors":"Daniel Álvarez,&nbsp;Hephzibah E Winter,&nbsp;Carlos J Velasquez Franco,&nbsp;Aleida Susana Castellanos Gutierrez,&nbsp;Núria Baños,&nbsp;Udo R Markert,&nbsp;Ángela P Cadavid,&nbsp;Diana M Morales-Prieto","doi":"10.1002/cti2.70021","DOIUrl":"10.1002/cti2.70021","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Antiphospholipid syndrome (APS) is an autoimmune disease driven by antiphospholipid antibodies (aPL). Currently, APS diagnosis requires a combination of clinical manifestations (thrombosis and/or obstetric morbidity) and the persistent presence of at least one criteria aPL: anti-cardiolipin antibodies (aCL), anti-β2-glycoprotein I antibodies (aβ2GPI) or lupus anticoagulant (LA). Patients with suggestive obstetric symptoms but lacking criteria aPL face diagnostic challenges. Non-criteria aPL screening may enhance discrimination. This study proposes a classification incorporating both criteria and non-criteria antibodies to improve obstetric APS diagnosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Blood samples from non-pregnant women (<i>n</i> = 68) with a history of vascular, obstetric, or vascular and obstetric manifestations were analysed. Among them, 30 had previous diagnosis of APS. Healthy women with proven gestational success were included as controls (<i>n</i> = 16). Criteria and non-criteria (anti-phosphatidylglycerol, anti-phosphatidylethanolamine, anti-phosphatidylinositol, anti-phosphatidylserine and anti-phosphatidic acid) IgG aPL were evaluated by ELISA and coagulation tests. Based on the resulting aPL profile, patients were reclassified. Responsiveness to treatment was obtained from medical records.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Criteria aPL levels marginally differentiated women previously managed as obstetric APS from unexplained/other causes of obstetric morbidity. Including non-criteria aPL improved separation. The proposed classification identified an obstetric APS group that exhibits non-criteria aPL and aβ2GPI titres below the cut-off but higher than healthy women (7.88 vs. 2.47 SGU, <i>P</i> = 0.006). Compared to cases of other causes of obstetric morbidity, these patients retrospectively responded better to aspirin and/or heparin treatment (71.43% vs. 11.11%, <i>P</i> = 0.035).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Assessing non-criteria antibodies may identify isolated obstetric APS cases benefiting from established therapies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 12","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11638733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826958","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 the bench to the clinic: basophils and type 2 epithelial cytokines of thymic stromal lymphopoietin and IL-33","authors":"Kazushige Obata-Ninomiya,&nbsp;Tharmalingam Jayaraman,&nbsp;Steven F Ziegler","doi":"10.1002/cti2.70020","DOIUrl":"10.1002/cti2.70020","url":null,"abstract":"<p>Type 2 epithelial cytokines, including thymic stromal lymphopoietin and IL-33, play central roles in modulation of type 2 immune cells, such as basophils. Basophils are a small subset of granulocytes within the leukocyte population that predominantly exist in the blood. They have non-redundant roles in allergic inflammation in peripheral tissues such as the lung, skin and gut, where they increase and accumulate at inflammatory lesions and exclusively produce large amounts of IL-4, a type 2 cytokine. These inflammatory reactions are known to be, to some extent, phenocopies of infectious diseases of ticks and helminths. Recently, biologics related to both type 2 epithelial cytokines and basophils have been approved by the US Food and Drug Administration for treatment of allergic diseases. We summarised the roles of Type 2 epithelial cytokines and basophils in basic science to translational medicine, including recent findings.</p>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 12","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11626414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798778","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":"Squamous cell carcinoma is associated with reduced IL34 expression, alterations in the Langerhans cell antigen-processing-presentation machinery and poor patient survival","authors":"Thi Viet Trinh Dang,&nbsp;Kevin R Gillinder,&nbsp;Quan Nguyen,&nbsp;Onkar Mulay,&nbsp;Tuan Vo,&nbsp;Ahmed M Mehdi,&nbsp;Chenhao Zhou,&nbsp;Andrew J Brooks,&nbsp;Graham R Leggatt,&nbsp;David A Hume,&nbsp;Ian H Frazer,&nbsp;Janin Chandra","doi":"10.1002/cti2.70018","DOIUrl":"https://doi.org/10.1002/cti2.70018","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Langerhans cells (LCs) are epithelial antigen-presenting cells (APC) contributing to immune surveillance. LCs depend on interleukin 34 (IL34) production by epithelial cells. This study aimed to uncover mechanisms of alteration of IL34 and LC function in squamous cell carcinoma (SCC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Cancer cohort data were used to identify associations between SCC and IL34. ATAC-seq of keratinocytes (KCs) and LCs from a murine model of epithelial hyperplasia, driven by HPV16 E7 oncoprotein (K14E7), was analysed. Transcriptomic data were used to validate findings. RNAscope, RT-qPCR, ELISA and confocal imaging was used to analyse IL34 expression and LCs in a spatial context.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p><i>IL34</i> mRNA is downregulated in human SCCs of the head and neck, the cervix, the lung and the oesophagus, and low <i>IL34</i> expression is associated with poor survival. We demonstrate that KCs of K14E7 mice have reduced <i>Il34</i> gene accessibility, mRNA and protein, as well as broad changes in promotor accessibility associated with cell adhesion and immune responses. Chromatin accessibility was substantially changed in LCs, including increased accessibility of the <i>Csf1r</i> gene, and changes in promotors associated with cytoskeleton arrangement and antigen processing and presentation. We discovered altered spatial LC dendrite organisation in hyperproliferative epithelium.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Squamous cell carcinoma of the cervix, head and neck, oesophagus and lung demonstrate downregulation of IL34, which is associated with poor survival, and with alterations in LC spatial organisation and function. These findings suggest that reduced IL34 expression in SCC may contribute to impaired local immunity through LC dysregulation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 12","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749098","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":"Choice of activation protocol impacts the yield and quality of CAR T cell product, particularly with older individuals","authors":"Palak H Mehta,&nbsp;Gemma S Trollope,&nbsp;Patrick Leung,&nbsp;Shivali Savita Chinni,&nbsp;Anna Iasinskaia,&nbsp;Aaron J Harrison,&nbsp;Hannah Hughes-Parry,&nbsp;Misty R Jenkins,&nbsp;Michael H Kershaw,&nbsp;Anthony Jaworowski,&nbsp;Clare Y Slaney,&nbsp;Rachel M Koldej,&nbsp;David S Ritchie,&nbsp;Kylie M Quinn","doi":"10.1002/cti2.70016","DOIUrl":"https://doi.org/10.1002/cti2.70016","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>In clinical chimeric antigen receptor (CAR) T cell therapy, one of the strongest correlates of favorable patient responses is lower levels of differentiation in T cells from the peripheral blood mononuclear cell (PBMC) starting material or the CAR T cell product. T cells from older patients are inherently more differentiated, but we hypothesised that specific activation protocols could be used to limit CAR T cell differentiation during manufacturing, particularly in older patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used PBMCs from young (20–30 years old) and older (60+ years old) healthy donors to generate CAR T cells using two activation protocols: soluble anti-(α) CD3 monoclonal antibody (mAb) <i>vs</i> immune complexes of αCD3 and αCD28 mAbs. Products were assessed for yield, function and differentiation, which was used as a measure of CAR T cell quality. T cells in PBMCs were assessed for CD28 expression and correlative analyses were performed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Older samples generated fewer, more differentiated CAR T cells than young samples, and the αCD3/CD28 mAb protocol exacerbated this, further reducing yield and quality. CD28 expression by T cells correlated with CAR T cell differentiation, but T cell differentiation in PBMC starting material was a stronger correlate of CAR T cell differentiation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Choice of activation protocol can substantially impact on the yield and quality of CAR T cells during manufacturing. This is a key consideration for older patients whose samples already generate a poorer yield and lower quality of CAR T cells.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 12","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749365","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":"CD8+ T cell epitope conservation in emerging H5N1 viruses suggests global protection","authors":"Emma J Grant,&nbsp;Stephanie Gras","doi":"10.1002/cti2.70017","DOIUrl":"https://doi.org/10.1002/cti2.70017","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>The recent H5N1 avian influenza outbreak in the USA has sparked fresh fears of avian viruses causing the next pandemic. To date, the H5N1 (clade 2.3.4.4b) outbreak in cattle has spread across several states in the USA, with several humans infected following exposure to cows. This H5N1 clade is also reportedly circulating across Europe, Africa and South America. H5N1 was also detected in a child returning to Australia following travel in India where H5N1 (clade 2.3.2.1a) is also reported to be circulating. There are no licenced vaccines against H5N1 avian influenza viruses for humans. Current vaccines aim to protect against seasonal H1N1 and H3N2 variants are unlikely to provide much protection against the different H5, or other avian viruses. CD8⁺ T cells are known to provide protection against influenza infection, enhancing viral control and decreasing disease severity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We recently compiled and published a list of the known immunogenic influenza-derived CD8⁺ T cell epitopes restricted to the most prevalent 10 HLA-A, -B and -C molecules worldwide. We assessed the conservation of a curated list of these influenza A virus-derived CD8⁺ T cell epitopes in H5N1 viruses' sequences at the heart of the outbreak.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified that &gt; 64% of the CD8⁺ T cell epitopes are highly conserved (&gt; 90% sequence identity) in the H5N1 viruses, with 60% (18/30) of the most prevalent HLA-I molecules have at least one immunogenic CD8⁺ T cell epitope conserved in H5N1 viruses. Together these HLA-I molecules with conserved epitopes have a cumulative total of &gt; 100% global coverage. Epitopes derived from the NP, M1, PB2, NS1 and PB1 proteins displayed the highest level of conservation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Together, this analysis highlights that globally there is the potential for T cell cross-recognition against the H5N1 viruses that may provide some protection in humans towards the current avian flu outbreak.</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/cti2.70017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142707677","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":"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}