Immunotherapy advances最新文献

{"title":"DNAM1 and TIGIT balance the T cell response, with low T cell TIGIT expression corresponding to inflammation in psoriatic disease","authors":"M. Jacobs, J. Pouw, M. O. Olde Nordkamp, T. Radstake, E. Leijten, M. Boes","doi":"10.1093/immadv/ltaa004","DOIUrl":"https://doi.org/10.1093/immadv/ltaa004","url":null,"abstract":"Summary Objectives Signals at the contact site of antigen-presenting cells (APCs) and T cells help orchestrate the adaptive immune response. CD155 on APCs can interact with the stimulatory receptor DNAM1 or inhibitory receptor TIGIT on T cells. The CD155/DNAM1/TIGIT axis is under extensive investigation as immunotherapy target in inflammatory diseases including cancer, chronic infection and autoimmune diseases. We investigated a possible role for CD155/DNAM1/TIGIT signaling in psoriatic disease. Methods By flow cytometry, we analyzed peripheral blood mononuclear cells of patients with psoriasis (n = 20) or psoriatic arthritis (n = 21), and healthy individuals (n = 7). We measured CD155, TIGIT, and DNAM1 expression on leukocyte subsets and compared activation-induced cytokine production between CD155-positive and CD155-negative APCs. We assessed the effects of TIGIT and DNAM1 blockade on T cell activation, and related the expression of CD155/DNAM1/TIGIT axis molecules to measures of disease activity. Results High CD155 expression associates with tumor necrosis factor (TNF) production in myeloid and plasmacytoid dendritic cells (DC). In CD1c+ myeloid DC, activation-induced CD155 expression associates with increased HLA-DR expression. CD8 T cells – but not CD4 T cells – express high levels of TIGIT. DNAM1 blockade decreases T cell pro-inflammatory cytokine production, while TIGIT blockade increased T cell proliferation. Finally, T cell TIGIT expression shows an inverse correlation with inflammation biomarkers in psoriatic disease. Conclusion CD155 is increased on pro-inflammatory APCs, while the receptors DNAM1 and TIGIT expressed on T cells balance the inflammatory response by T cells. In psoriatic disease, low TIGIT expression on T cells is associated with systemic inflammation.","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/immadv/ltaa004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44775105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Introducing <i>Immunotherapy Advances</i>.","authors":"Tim Elliott","doi":"10.1093/immadv/ltaa009","DOIUrl":"10.1093/immadv/ltaa009","url":null,"abstract":"","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2020-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9585662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42904584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CAR-T cells leave the comfort zone: current and future applications beyond cancer.","authors":"Mariana Torres Mazzi, Karina Lôbo Hajdu, Priscila Rafaela Ribeiro, Martín Hernán Bonamino","doi":"10.1093/immadv/ltaa006","DOIUrl":"10.1093/immadv/ltaa006","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR)-T cell therapy represents a breakthrough in the immunotherapy field and has achieved great success following its approval in 2017 for the treatment of B cell malignancies. While CAR-T cells are mostly applied as anti-tumor therapy in the present, their initial concept was aimed at a more general purpose of targeting membrane antigens, thus translating in many potential applications. Since then, several studies have assessed the use of CAR-T cells toward non-malignant pathologies such as autoimmune diseases, infectious diseases and, more recently, cardiac fibrosis, and cellular senescence. In this review, we present the main findings and implications of CAR-based therapies for non-malignant conditions.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2020-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9585679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47060434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitamin D₃ replacement enhances antigen-specific immunity in older adults.","authors":"Emma S Chambers, Milica Vukmanovic-Stejic, Carolin T Turner, Barbara B Shih, Hugh Trahair, Gabriele Pollara, Evdokia Tsaliki, Malcolm Rustin, Tom C Freeman, Neil A Mabbott, Mahdad Noursadeghi, Adrian R Martineau, Arne N Akbar","doi":"10.1093/immadv/ltaa008","DOIUrl":"10.1093/immadv/ltaa008","url":null,"abstract":"<p><strong>Introduction: </strong>Ageing is associated with increased number of infections, decreased vaccine efficacy and increased systemic inflammation termed inflammageing. These changes are reflected by reduced recall responses to varicella zoster virus (VZV) challenge in the skin of older adults. Vitamin D deficiency is more common in the old and has been associated with frailty and increased inflammation. In addition, vitamin D increases immunoregulatory mechanisms and therefore has the potential to inhibit inflammageing.</p><p><strong>Objectives: </strong>We investigated the use of vitamin D₃ replacement to enhance cutaneous antigen-specific immunity in older adults (≥65 years).</p><p><strong>Methods: </strong>Vitamin D insufficient older adults (<i>n</i> = 18) were administered 6400IU of vitamin D₃/day orally for 14 weeks. Antigen-specific immunity to VZV was assessed by clinical score assessment of the injection site and transcriptional analysis of skin biopsies collected from challenged injection sites pre- and post-vitamin D₃ replacement.</p><p><strong>Results: </strong>We showed that older adults had reduced VZV-specific cutaneous immune response and increased non-specific inflammation as compared to young. Increased non-specific inflammation observed in the skin of older adults negatively correlated with vitamin D sufficiency. We showed that vitamin D₃ supplementation significantly increased the response to cutaneous VZV antigen challenge in older adults. This enhancement was associated with a reduction in inflammatory monocyte infiltration with a concomitant enhancement of T cell recruitment to the site of antigen challenge in the skin.</p><p><strong>Conclusion: </strong>Vitamin D₃ replacement can boost antigen-specific immunity in older adults with sub-optimal vitamin D status.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2020-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9585673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9264401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting clinical response to costimulation blockade in autoimmunity.","authors":"Natalie M Edner,&nbsp;Chun Jing Wang,&nbsp;Lina Petersone,&nbsp;Lucy S K Walker","doi":"10.1093/immadv/ltaa003","DOIUrl":"https://doi.org/10.1093/immadv/ltaa003","url":null,"abstract":"<p><p>Curbing unwanted T cell responses by costimulation blockade has been a recognised immunosuppressive strategy for the last 15 years. However, our understanding of how best to deploy this intervention is still evolving. A key challenge has been the heterogeneity in the clinical response to costimulation blockade, and an inability to predict which individuals are likely to benefit most. Here, we discuss our recent findings based on the use of costimulation blockade in people with type 1 diabetes (T1D) and place them in the context of the current literature. We discuss how profiling follicular helper T cells (Tfh) in pre-treatment blood samples may have value in predicting which individuals are likely to benefit from costimulation blockade drugs such as abatacept.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7613378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33438193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances in immunotherapies against infectious diseases.","authors":"Dharanidharan Ramamurthy, Trishana Nundalall, Sanele Cingo, Neelakshi Mungra, Maryam Karaan, Krupa Naran, Stefan Barth","doi":"10.1093/immadv/ltaa007","DOIUrl":"10.1093/immadv/ltaa007","url":null,"abstract":"<p><p>Immunotherapies are disease management strategies that target or manipulate components of the immune system. Infectious diseases pose a significant threat to human health as evidenced by countries continuing to grapple with several emerging and re-emerging diseases, the most recent global health threat being the SARS-CoV2 pandemic. As such, various immunotherapeutic approaches are increasingly being investigated as alternative therapies for infectious diseases, resulting in significant advances towards the uncovering of pathogen-host immunity interactions. Novel and innovative therapeutic strategies are necessary to overcome the challenges typically faced by existing infectious disease prevention and control methods such as lack of adequate efficacy, drug toxicity, and the emergence of drug resistance. As evidenced by recent developments and success of pharmaceuticals such as monoclonal antibodies (mAbs), immunotherapies already show abundant promise to overcome such limitations while also advancing the frontiers of medicine. In this review, we summarize some of the most notable inroads made to combat infectious disease, over mainly the last 5 years, through the use of immunotherapies such as vaccines, mAb-based therapies, T-cell-based therapies, manipulation of cytokine levels, and checkpoint inhibition. While its most general applications are founded in cancer treatment, advances made towards the curative treatment of human immunodeficiency virus, tuberculosis, malaria, zika virus and, most recently COVID-19, reinforce the role of immunotherapeutic strategies in the broader field of disease control. Ultimately, the comprehensive specificity, safety, and cost of immunotherapeutics will impact its widespread implementation.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43228724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective low-avidity anti-tumour CD8+ T cells are selectively attenuated by regulatory T cells.","authors":"Gessa Sugiyarto,&nbsp;David Prossor,&nbsp;Osman Dadas,&nbsp;E David Arcia-Anaya,&nbsp;Tim Elliott,&nbsp;Edward James","doi":"10.1093/immadv/ltaa001","DOIUrl":"https://doi.org/10.1093/immadv/ltaa001","url":null,"abstract":"<p><strong>Objectives: </strong>Regulatory T cells (Treg) play a major role in the suppression of protective anti-tumour T cell responses. In the CT26 BALB/c murine model of colorectal carcinoma, Tregs differentially suppress responses to two characterised CD8+ T epitopes, AH1 and GSW11, which results in an absence of detectable IFN-γ-producing GSW11-specific T cells in the spleen and lymph nodes of tumour challenged mice. Activation of GSW11-specific T cells correlates with protection against tumour progression. We wanted to examine the presence of non-functional GSW11-specific T cells in Treg replete and depleted mice, assess their phenotype and their affinity compared to AH1-specific T cells.</p><p><strong>Methods: </strong>We used peptide-specific tetramers to identify tumour-specific CD8+ T cells and assessed the cell surface expression of markers associated with exhaustion (PD-1, Tim3 and Lag-3) and their function by IFN-g production using flow cytometry. We also assessed the T cell receptor (TcR) clonality of tumour-specific T cells. Tetramer competition assays were performed to determine the relative affinity of identified TcR.</p><p><strong>Results: </strong>Here, we show that GSW11-specific T cells are in fact induced in Treg-replete, CT26-bearing mice, where they make up the majority of tumour-infiltrating CD8+ lymphocytes, but exhibit an 'exhausted' phenotype. This dysfunctional phenotype is induced early in the anti-tumour response in tumours. Depletion of Tregs prior to tumour challenge correlates with an altered T cell receptor (TcR) repertoire. Moreover, the avidity of GSW11-specific TcRs that expanded in the absence of Tregs was significantly lower compared with TcRs of CD8+populations that were diminished in protective anti-tumour responses.</p><p><strong>Conclusion: </strong>Our results indicate that Tregs suppress the induction of protective anti-tumour T cell responses and may signify that low-avidity T cells play an important role in this protection.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/immadv/ltaa001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25502130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The MARVEL trial: a phase 2b randomised placebo-controlled trial of oral MitoQ in moderate ulcerative colitis","authors":"Emily Gwyer Findlay, G. Sutton, G. Ho","doi":"10.1093/immadv/ltaa002","DOIUrl":"https://doi.org/10.1093/immadv/ltaa002","url":null,"abstract":"Summary Ulcerative colitis (UC) is an inflammatory disease of the large bowel which is characterised by dysregulated immunity and death to epithelial cells in the bowel, leading to prolonged inflammation. This can ultimately lead to surgery to remove the large bowel, with a risk of cancer developing if inflammation persists. Current therapies – which target the incoming immune cells or the cytokines they produce – are improving significantly but they are expensive and are immunosuppressive, leading to risk of infection. Here, we discuss a new trial which targets an early inducer of inflammation – the production of reactive oxygen species (ROS) by mitochondria. Previous work has shown that excessive mitochondrial ROS induces inflammatory signalling through the cGAS-STING pathway, leading to dysregulated immunity and death of epithelial cells. In this MARVEL trial (Mitochondrial Anti-oxidant therapy to Resolve Inflammation in Ulcerative Colitis) individuals with an active UC flare-up will be given a mitochondrial anti-oxidant (MitoQ) or placebo tablet in addition to standard medical treatment, in order to suppress inflammation as it develops. This phase 2b trial will repurpose MitoQ, which has been previously tested in other large trials in different disease settings, and will measure clinical response and markers of inflammation over 24 weeks. It is hoped that this trial will develop a new target for UC through re-purposing a relatively cheap, non-toxic and well-characterised drug.","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47880806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}