Cellular immunology最新文献

{"title":"Enhancing antitumor response by efficiently generating large-scale TCR-T cells targeting a single epitope across multiple cancer antigens","authors":"Obed Boadi Amissah ,&nbsp;Rajesh Basnet ,&nbsp;Wenfang Chen ,&nbsp;Jean de Dieu Habimana ,&nbsp;Belinda Edwina Baiden ,&nbsp;Osei Asibey Owusu ,&nbsp;Babangida Jabir Saeed ,&nbsp;Zhiyuan Li","doi":"10.1016/j.cellimm.2024.104827","DOIUrl":"https://doi.org/10.1016/j.cellimm.2024.104827","url":null,"abstract":"<div><p>The need to contrive interventions to curb the rise in cancer incidence and mortality is critical for improving patients’ prognoses. Adoptive cell therapy is challenged with quality large-scale production, heightening its production cost.</p><p>Several cancer types have been associated with the expression of highly-immunogenic CTAG1 and CTAG2 antigens, which share common epitopes. Targeting two antigens on the same cancer could improve the antitumor response of TCR-T cells.</p><p>In this study, we exploited an efficient way to generate large-fold quality TCR-T cells and also demonstrated that the common epitopes of CTAG1 and CTAG2 antigens provide an avenue for improved cancer-killing via dual-antigen-epitope targeting.</p><p>Our study revealed that xeno/sera-free medium could expand TCR-T cells to over 500-fold, posing as a better replacement for FBS-supplemented media. Human AB serum was also shown to be a good alternative in the absence of xeno/sera-free media. Furthermore, TCR-T cells stimulated with beads-coated <em>T</em>-activator showed a better effector function than soluble <em>T</em>-activator stimulated TCR-T cells. Additionally, TCR-T cells that target multiple antigens in the same cancer yield better anticancer activity than those targeting a single antigen. This showed that targeting multiple antigens with a common epitope may enhance the antitumor response efficacy of T cell therapies.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"399 ","pages":"Article 104827"},"PeriodicalIF":4.3,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140906476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leishmania vaccine development: A comprehensive review","authors":"Isha Saini ,&nbsp;Jyoti Joshi ,&nbsp;Sukhbir Kaur","doi":"10.1016/j.cellimm.2024.104826","DOIUrl":"https://doi.org/10.1016/j.cellimm.2024.104826","url":null,"abstract":"<div><p>Infectious diseases like leishmaniasis, malaria, HIV, tuberculosis, leprosy and filariasis are responsible for an immense burden on public health systems. Among these, leishmaniasis is under the category I diseases as it is selected by WHO (World Health Organization) on the ground of diversity and complexity. High cost, resistance and toxic effects of <em>Leishmania</em> traditional drugs entail identification and development of therapeutic alternative. Since the natural infection elicits robust immunity, consistence efforts are going on to develop a successful vaccine. Clinical trials have been conducted on vaccines like Leish-F1, F2, and F3 formulated using specific <em>Leishmania</em> antigen epitopes. Current strategies utilize individual or combined antigens from the parasite or its insect vector's salivary gland extract, with or without adjuvant formulation for enhanced efficacy. Promising animal data supports multiple vaccine candidates (Lmcen-/-, LmexCen^−/−), with some already in or heading for clinical trials. The crucial challenge in <em>Leishmania</em> vaccine development is to translate the research knowledge into affordable and accessible control tools that refines the outcome for those who are susceptible to infection. This review focuses on recent findings in <em>Leishmania</em> vaccines and highlights difficulties facing vaccine development and implementation.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"399 ","pages":"Article 104826"},"PeriodicalIF":4.3,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140645690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophage niche imprinting as a determinant of macrophage identity and function","authors":"Malgorzata Kloc ,&nbsp;Marta Halasa ,&nbsp;Rafik M. Ghobrial","doi":"10.1016/j.cellimm.2024.104825","DOIUrl":"https://doi.org/10.1016/j.cellimm.2024.104825","url":null,"abstract":"<div><p>Macrophage niches are the anatomical locations within organs or tissues consisting of various cells, intercellular and extracellular matrix, transcription factors, and signaling molecules that interact to influence macrophage self-maintenance, phenotype, and behavior. The niche, besides physically supporting macrophages, imposes a tissue- and organ-specific identity on the residing and infiltrating monocytes and macrophages. In this review, we give examples of macrophage niches and the modes of communication between macrophages and surrounding cells. We also describe how macrophages, acting against their immune defensive nature, can create a hospitable niche for pathogens and cancer cells.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"399 ","pages":"Article 104825"},"PeriodicalIF":4.3,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140621834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of innate and adaptive immunity to RSV in young children","authors":"Emily L. Parsons ,&nbsp;Jisung S. Kim ,&nbsp;Allison M.W. Malloy","doi":"10.1016/j.cellimm.2024.104824","DOIUrl":"10.1016/j.cellimm.2024.104824","url":null,"abstract":"<div><p>Infection of the respiratory tract with respiratory syncytial virus (RSV) is common and occurs repeatedly throughout life with most severe disease occurring at the extremes of age: in young infants and the elderly. Effective anti-viral therapeutics are not available and therefore prevention has been the primary strategy for reducing the disease burden. Our current understanding of respiratory mucosal cell biology and the immune response within the respiratory tract is inadequate to prevent infection caused by a pathogen like RSV that does not disseminate outside of this environment. Gaps in our understanding of the activation of innate and adaptive immunity in response to RSV and the role of age upon infection also limit improvements in the design of therapeutics and vaccines for young infants. However, advancements in structural biology have improved our ability to characterize antibodies against viral proteins and in 2023 the first vaccines for those over 60 years and pregnant women became available, potentially reducing the burden of disease. This review will examine our current understanding of the critical facets of anti-RSV immune responses in infants and young children as well as highlight areas where more research is needed.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"399 ","pages":"Article 104824"},"PeriodicalIF":4.3,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140400185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The presence of CpGs in AAV gene therapy vectors induces a plasmacytoid dendritic cell-like population very early after administration","authors":"Justin D. Glenn,&nbsp;Henos Negash,&nbsp;William Henry,&nbsp;Randolph Qian,&nbsp;Ye Liu,&nbsp;Olivier Danos,&nbsp;Joseph T. Bruder,&nbsp;Subha Karumuthil-Melethil","doi":"10.1016/j.cellimm.2024.104823","DOIUrl":"10.1016/j.cellimm.2024.104823","url":null,"abstract":"<div><p>AAV-mediated gene transfer is a promising platform still plagued by potential host-derived, antagonistic immune responses to therapeutic components. CpG-mediated TLR9 stimulation activates innate immune cells and leads to cognate T cell activation and suppression of transgene expression. Here, we demonstrate that CpG depletion increased expression of an antibody transgene product by 2–3-fold as early as 24 h post-vector administration in mice. No significant differences were noted in anti-transgene product/ anti-AAV capsid antibody production or cytotoxic gene induction. Instead, CpG depletion significantly reduced the presence of a pDC-like myeloid cell population, which was able to directly bind the antibody transgene product via Fc-FcγR interactions. Thus, we extend the mechanisms of TLR9-mediated antagonism of transgene expression in AAV gene therapy to include the actions of a previously unreported pDC-like cell population.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"399 ","pages":"Article 104823"},"PeriodicalIF":4.3,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140181778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HLA-class-I expression loss, tumor microenvironment and breast cancer prognosis","authors":"Alexandra Giatromanolaki ,&nbsp;Georgios D. Michos ,&nbsp;Erasmia Xanthopoulou ,&nbsp;Michael I. Koukourakis","doi":"10.1016/j.cellimm.2024.104816","DOIUrl":"10.1016/j.cellimm.2024.104816","url":null,"abstract":"<div><p>Loss of HLA-class-I molecule expression by cancer cells is a frequent event in human tumors that may lead to immune evasion from cytotoxic <em>T</em>-cells. We examined the expression patterns of HLA-class-I molecules in a series of 175 patients with operable breast cancer (BCa). Extensive loss of BCa cell HLA-class-I expression was noted 76.6 % of patients (27.5 % complete loss). A significant association of HLA-preservation with high TIL-density (p = 0.001) was documented. Preservation of HLA was evident only in BCa carcinomas with low HIF1α expression and high TIL-density. Cell line experiments (MCF7 and T47D) showed that induction of HLAs in cancer cells following incubation with lymphocytes or IFNγ, was abrogated under hypoxic conditions. HLA-preservation was linked with better distant metastasis-free survival (p = 0.01), which was confirmed also in multivariate analysis (p = 0.02, HR 3.17). Studying the expression of HLA-class-I molecules in parallel with TIL-density and HIF1α expression may identify subgroups of BCa patients who would benefit from immunotherapy.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"399 ","pages":"Article 104816"},"PeriodicalIF":4.3,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140056050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of the major immune differences in severe asthmatic children according to their atopic dermatitis status","authors":"Guillaume Lezmi ,&nbsp;Clément Poirault ,&nbsp;Marta Grauso ,&nbsp;Céline Dietrich ,&nbsp;Karine Adel-Patient ,&nbsp;Maria Leite-de-Moraes","doi":"10.1016/j.cellimm.2024.104815","DOIUrl":"https://doi.org/10.1016/j.cellimm.2024.104815","url":null,"abstract":"<div><p>Severe asthma (SA) affects 2% to 5% of asthmatic children. Atopic dermatitis can affect up to 34% of children with SA (cwSA). Atopic dermatitis and asthma share common genetic and immunological features. However, not all children with SA suffer from AD, and it remains unclear whether the overall immune profiles of these children are similar. In this study, seventeen cwSA (9.8 [7.1–13.2] years; seven with and ten without AD) were enrolled. Bronchoalveolar lavage (BAL) and blood samples were collected from these patients. Seventy-three cytokines/chemokines and distinct immune T cell populations were evaluated in blood and BAL. We found that BAL and blood immune profiles of cwSA with and without AD were globally similar. However, specific differences were observed, namely lower frequency of Tc2, Th17 and IL-17-producing mucosal associated invariant T (MAIT-17) cells and higher CD8/CD4 ratio and IL-22 concentrations in BAL and of CCL19 concentrations in plasma from cwSA with AD. Further, in contrast with cwSA without AD, we found a positive correlation between a set of plasma cytokines and almost all cytokines in BAL in cwSA with AD. In conclusion, this study shows the major immune differences between cwSA with and without AD in BAL and blood suggesting that distinct endotypes may be implicated in the inflammatory responses observed in these pediatric patients.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"397 ","pages":"Article 104815"},"PeriodicalIF":4.3,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139999627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MALT1 inhibition suppresses antigen-specific T cell responses","authors":"Iliana K. Kerzeli ,&nbsp;Aikaterini Nasi ,&nbsp;Erika Fletcher ,&nbsp;Aikaterini Chourlia ,&nbsp;Anders Kallin ,&nbsp;Niklas Finnberg ,&nbsp;Karolina Ersmark ,&nbsp;Maria Lampinen ,&nbsp;Mark Albertella ,&nbsp;Fredrik Öberg ,&nbsp;Sara M. Mangsbo","doi":"10.1016/j.cellimm.2024.104814","DOIUrl":"https://doi.org/10.1016/j.cellimm.2024.104814","url":null,"abstract":"<div><p>The aim of this study was to assess the potential use of a selective small molecule MALT1 inhibitor in solid tumor treatment as an immunotherapy targeting regulatory <em>T</em>-cells (Tregs). In vitro, MALT1 inhibition suppressed the proteolytic cleavage of the MALT1-substrate HOIL1 and blocked IL-2 secretion in Jurkat cells. It selectively suppressed the proliferation of PBMC-derived Tregs, with no effect on conventional CD4⁺ <em>T</em>-cells. In vivo, however, no evident anti-tumor effect was achieved by MALT1 inhibition monotherapy or in combination with anti-CTLA4 in the MB49 cancer model. Despite decreased Treg-frequencies in lymph nodes of tumor-bearing animals, intratumoral Treg depletion was not observed. We also showed that MALT1-inhibition caused a reduction of antigen-specific CD8⁺ <em>T</em>-cells in an adoptive <em>T</em>-cell transfer model. Thus, selective targeting of Tregs would be required to improve the immunotherapeutic effect of MALT1-inhibition. Also, various dosing schedules and combination therapy strategies should be carefully designed and evaluated further.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"397 ","pages":"Article 104814"},"PeriodicalIF":4.3,"publicationDate":"2024-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0008874924000170/pdfft?md5=62eb291a5ca460edaa986e72945f54c4&pid=1-s2.0-S0008874924000170-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139985895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic potential of mesenchymal stem cell-derived exosomes for allergic airway inflammation","authors":"Mahvash Sadeghi ,&nbsp;Mojgan Mohammadi ,&nbsp;Jalil Tavakol Afshari ,&nbsp;Sara Iranparast ,&nbsp;Bahareh Ansari ,&nbsp;Sajad Dehnavi","doi":"10.1016/j.cellimm.2024.104813","DOIUrl":"https://doi.org/10.1016/j.cellimm.2024.104813","url":null,"abstract":"<div><p>Due to their immunomodulatory capacities, mesenchymal stem cells (MSCs) have been extensively used as therapeutic approaches in cell-based therapy for various inflammatory diseases. Several lines of studies have shown that the most beneficial effects of MSCs are associated with MSC-derived exosomes. Exosomes are nanoscale extracellular vesicles that contain important biomolecules such as RNA, microRNAs (miRNAs), DNA, growth factors, enzymes, chemokines, and cytokines that regulate immune cell functions and parenchymal cell survival. Recently, exosomes, especially MSC-derived exosomes, have been shown to have protective effects in allergic airway inflammation. This review focused on the immune-regulatory potential of MSC-derived exosomes as nanoscale delivery systems in the treatment of allergic airway inflammation.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"397 ","pages":"Article 104813"},"PeriodicalIF":4.3,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139743895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Helicobacter pylori secretary Proteins-Induced oxidative stress and its role in NLRP3 inflammasome activation","authors":"Sandeep Kumar ,&nbsp;Monisha Dhiman","doi":"10.1016/j.cellimm.2024.104811","DOIUrl":"10.1016/j.cellimm.2024.104811","url":null,"abstract":"&lt;div&gt;&lt;p&gt;&lt;em&gt;Helicobacter pylori&lt;/em&gt;-associated stomach infection is a leading cause of gastric ulcer and related cancer. &lt;em&gt;H. pylori&lt;/em&gt; modulates the functions of infiltrated immune cells to survive the killing by reactive oxygen and nitrogen species (ROS and RNS) produced by these cells. Uncontrolled immune responses further produce excess ROS and RNS which lead to mucosal damage. The persistent oxidative stress is a major cause of gastric cancer. &lt;em&gt;H. pylori&lt;/em&gt; regulates nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs), nitric oxide synthase 2 (NOS2), and polyamines to control ROS and RNS release through lesser-known mechanisms. ROS and RNS produced by these pathways differentiate macrophages and T cells from protective to inflammatory phenotype. Pathogens-associated molecular patterns (PAMPs) induced ROS activates nuclear oligomerization domain (NOD), leucine rich repeats (LRR) and pyrin domain-containing protein 3 (NLRP3) inflammasome for the release of pro-inflammatory cytokines. This study evaluates the role of &lt;em&gt;H. pylori&lt;/em&gt; secreted concentrated proteins (HPSCP) related oxidative stress role in NLRP3 inflammasome activation and macrophage differentiation. To perceive the role of ROS/RNS, THP-1 and AGS cells were treated with 10 μM diphenyleneiodonium (DPI), 50 μM salicyl hydroxamic acid (SHX), 5 μM Carbonyl cyanide-4-(trifluoromethoxy) phenylhydrazone (FCCP), which are specific inhibitors of NADPH oxidase (NOX), Myeloperoxidase (MPO), and mitochondrial oxidative phosphorylation respectively. Cells were also treated with 10 μM of NOS2 inhibitor &lt;span&gt;l&lt;/span&gt;-NMMA and 10 μM of &lt;em&gt;N&lt;/em&gt;-acetyl cysteine (NAC), a free radical scavenger·H&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;2&lt;/sub&gt; (100 μM) treated and untreated cells were used as positive controls and negative control respectively. The expression of gp91&lt;sup&gt;phox&lt;/sup&gt; (NOX2), NOS2, NLRP3, CD86 and CD163 was analyzed through fluorescent microscopy. THP-1 macrophages growth was unaffected whereas the gastric epithelial AGS cells proliferated in response to higher concentration of HPSCP. ROS and myeloperoxidase (MPO) level increased in THP-1 cells and nitric oxide (NO) and lipid peroxidation significantly decreased in AGS cells. gp91&lt;sup&gt;phox&lt;/sup&gt; expression was unchanged, whereas NOS2 and NLRP3 downregulated in response to HPSCP, but increased after inhibition of NO, ROS and MPO in THP-1 cells. HPSCP upregulated the expression of M1 and M2 macrophage markers, CD86 and CD163 respectively, which was decreased after the inhibition of ROS.&lt;/p&gt;&lt;p&gt;This study concludes that there are multiple pathways which are generating ROS during &lt;em&gt;H. pylori&lt;/em&gt; infection which further regulates other cellular processes. NO is closely associated with MPO and inhibition of NLRP3 inflammasome. The low levels of NO and MPO regulates gastrointestinal tract homeostasis and overcomes the inflammatory response of NLRP3. The ROS also plays crucial role in macrophage polarization hence alter the immune r","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"399 ","pages":"Article 104811"},"PeriodicalIF":4.3,"publicationDate":"2024-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139669313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}