Pub Date : 2024-06-12eCollection Date: 2024-01-01DOI: 10.1155/2024/4312908
Md Mijanur Rahman, I Darren Grice, Glen C Ulett, Ming Q Wei
Antigenic cell fragments, pathogen-associated molecular patterns, and other immunostimulants in bacterial lysates or extracts may induce local and systemic immune responses in specific and nonspecific paradigms. Based on current knowledge, this review aimed to determine whether bacterial lysate has comparable functions in infectious diseases and cancer treatment. In infectious diseases, including respiratory and urinary tract infections, immune system activation by bacterial lysate can identify and combat pathogens. Commercially available bacterial lysates, including OM-85, Ismigen, Lantigen B, and LW 50020, were effective in children and adults in treating respiratory tract infections, chronic obstructive pulmonary disease, rhinitis, and rhinosinusitis with varying degrees of success. Moreover, OM-89, Uromune, Urovac, Urivac, and ExPEC4V showed therapeutic benefits in controlling urinary tract infections in adults, especially women. Bacterial lysate-based therapeutics are safe, well-tolerated, and have few side effects, making them a good alternative for infectious disease management. Furthermore, a nonspecific immunomodulation by bacterial lysates may stimulate innate immunity, benefiting cancer treatment. "Coley's vaccine" has been used to treat sarcomas, carcinomas, lymphomas, melanomas, and myelomas with varying outcomes. Later, several similar bacterial lysate-based therapeutics have been developed to treat cancers, including bladder cancer, non-small cell lung cancer, and myeloma; among them, BCG for in situ bladder cancer is well-known. Proinflammatory cytokines, including IL-1, IL-6, IL-12, and TNF-α, may activate bacterial antigen-specific adaptive responses that could restore tumor antigen recognition and response by tumor-specific type 1 helper cells and cytotoxic T cells; therefore, bacterial lysates are worth investigating as a vaccination adjuvants or add-on therapies for several cancers.
细菌裂解物或提取物中的抗原细胞片段、病原体相关分子模式和其他免疫刺激物质可在特异性和非特异性范例中诱导局部和全身免疫反应。基于现有知识，本综述旨在确定细菌裂解物在感染性疾病和癌症治疗中是否具有类似功能。在感染性疾病（包括呼吸道和泌尿道感染）中，细菌裂解液激活的免疫系统可以识别和对抗病原体。市售细菌裂解液，包括 OM-85、Ismigen、Lantigen B 和 LW 50020，对儿童和成人的呼吸道感染、慢性阻塞性肺病、鼻炎和鼻窦炎都有不同程度的治疗效果。此外，OM-89、Uromune、Urovac、Urivac 和 ExPEC4V 在控制成人（尤其是女性）尿路感染方面也显示出治疗效果。细菌裂解物疗法安全、耐受性好、副作用小，是治疗感染性疾病的理想选择。此外，细菌裂解物的非特异性免疫调节作用可刺激先天性免疫，有利于癌症治疗。"科利疫苗 "曾被用于治疗肉瘤、癌、淋巴瘤、黑色素瘤和骨髓瘤，效果各异。后来，又开发了几种类似的细菌裂解物疗法来治疗癌症，包括膀胱癌、非小细胞肺癌和骨髓瘤；其中，卡介苗治疗原位膀胱癌是众所周知的。包括 IL-1、IL-6、IL-12 和 TNF-α 在内的促炎细胞因子可能会激活细菌抗原特异性适应性反应，从而恢复肿瘤特异性 1 型辅助细胞和细胞毒性 T 细胞对肿瘤抗原的识别和反应；因此，细菌裂解物作为疫苗佐剂或多种癌症的附加疗法值得研究。
{"title":"Advances in Bacterial Lysate Immunotherapy for Infectious Diseases and Cancer.","authors":"Md Mijanur Rahman, I Darren Grice, Glen C Ulett, Ming Q Wei","doi":"10.1155/2024/4312908","DOIUrl":"10.1155/2024/4312908","url":null,"abstract":"<p><p>Antigenic cell fragments, pathogen-associated molecular patterns, and other immunostimulants in bacterial lysates or extracts may induce local and systemic immune responses in specific and nonspecific paradigms. Based on current knowledge, this review aimed to determine whether bacterial lysate has comparable functions in infectious diseases and cancer treatment. In infectious diseases, including respiratory and urinary tract infections, immune system activation by bacterial lysate can identify and combat pathogens. Commercially available bacterial lysates, including OM-85, Ismigen, Lantigen B, and LW 50020, were effective in children and adults in treating respiratory tract infections, chronic obstructive pulmonary disease, rhinitis, and rhinosinusitis with varying degrees of success. Moreover, OM-89, Uromune, Urovac, Urivac, and ExPEC4V showed therapeutic benefits in controlling urinary tract infections in adults, especially women. Bacterial lysate-based therapeutics are safe, well-tolerated, and have few side effects, making them a good alternative for infectious disease management. Furthermore, a nonspecific immunomodulation by bacterial lysates may stimulate innate immunity, benefiting cancer treatment. \"Coley's vaccine\" has been used to treat sarcomas, carcinomas, lymphomas, melanomas, and myelomas with varying outcomes. Later, several similar bacterial lysate-based therapeutics have been developed to treat cancers, including bladder cancer, non-small cell lung cancer, and myeloma; among them, BCG for in situ bladder cancer is well-known. Proinflammatory cytokines, including IL-1, IL-6, IL-12, and TNF-<i>α</i>, may activate bacterial antigen-specific adaptive responses that could restore tumor antigen recognition and response by tumor-specific type 1 helper cells and cytotoxic T cells; therefore, bacterial lysates are worth investigating as a vaccination adjuvants or add-on therapies for several cancers.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2024 ","pages":"4312908"},"PeriodicalIF":3.5,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11221958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-07eCollection Date: 2024-01-01DOI: 10.1155/2024/6817965
Laís Teodoro Da Silva, Bruna Tiaki Tiyo, Silvia de Jesus Mota, Marina Mazzilli Ortega, Gabriela Justamante Handel Schmitz, Noemi Nosomi Taniwaki, Gislene Mitsue Namiyama Nishina, Alberto José da Silva Duarte, Telma Miyuki Oshiro
Therapeutic vaccines based on monocyte-derived dendritic cells have been shown to be promising strategies and may act as complementary treatments for viral infections, cancers, and, more recently, autoimmune diseases. Alpha-type-1-polarized dendritic cells (aDC1s) have been shown to induce type-1 immunity with a high capacity to produce interleukin-12p70 (IL-12p70). In the clinical use of cell-based therapeutics, injectable solutions can affect the morphology, immunophenotypic profile, and viability of cells before delivery and their survival after injection. In this sense, preparing a cell suspension that maintains the quality of aDC1s is essential to ensure effective immunotherapy. In the present study, monocytes were differentiated into aDC1s in the presence of IL-4 and GM-CSF. On day 5, the cells were matured by the addition of a cytokine cocktail consisting of IFN-α, IFN-γ, IL-1β, TNF-α, and Poly I:C. After 48 hr, mature aDC1s were harvested and suspended in two different solutions: normal saline and Ringer's lactate. The maintenance of cells in suspension was evaluated after 4, 6, and 8 hr of storage. Cell viability, immunophenotyping, and apoptosis analyses were performed by flow cytometry. Cellular morphology was observed by electron microscopy, and the production of IL-12p70 by aDC1s was evaluated by ELISA. Compared with normal saline, Ringer's lactate solution was more effective at maintaining DC viability for up to 8 hr of incubation at 4 or 22°C.
{"title":"Effects of Injectable Solutions on the Quality of Monocyte-Derived Dendritic Cells for Immunotherapy.","authors":"Laís Teodoro Da Silva, Bruna Tiaki Tiyo, Silvia de Jesus Mota, Marina Mazzilli Ortega, Gabriela Justamante Handel Schmitz, Noemi Nosomi Taniwaki, Gislene Mitsue Namiyama Nishina, Alberto José da Silva Duarte, Telma Miyuki Oshiro","doi":"10.1155/2024/6817965","DOIUrl":"10.1155/2024/6817965","url":null,"abstract":"<p><p>Therapeutic vaccines based on monocyte-derived dendritic cells have been shown to be promising strategies and may act as complementary treatments for viral infections, cancers, and, more recently, autoimmune diseases. Alpha-type-1-polarized dendritic cells (aDC1s) have been shown to induce type-1 immunity with a high capacity to produce interleukin-12p70 (IL-12p70). In the clinical use of cell-based therapeutics, injectable solutions can affect the morphology, immunophenotypic profile, and viability of cells before delivery and their survival after injection. In this sense, preparing a cell suspension that maintains the quality of aDC1s is essential to ensure effective immunotherapy. In the present study, monocytes were differentiated into aDC1s in the presence of IL-4 and GM-CSF. On day 5, the cells were matured by the addition of a cytokine cocktail consisting of IFN-<i>α</i>, IFN-<i>γ</i>, IL-1<i>β</i>, TNF-<i>α</i>, and Poly I:C. After 48 hr, mature aDC1s were harvested and suspended in two different solutions: normal saline and Ringer's lactate. The maintenance of cells in suspension was evaluated after 4, 6, and 8 hr of storage. Cell viability, immunophenotyping, and apoptosis analyses were performed by flow cytometry. Cellular morphology was observed by electron microscopy, and the production of IL-12p70 by aDC1s was evaluated by ELISA. Compared with normal saline, Ringer's lactate solution was more effective at maintaining DC viability for up to 8 hr of incubation at 4 or 22°C.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2024 ","pages":"6817965"},"PeriodicalIF":3.5,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11221978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Noe Juvenal Mendoza-Ramírez, Julio García-Cordero, Gaurav Shrivastava, Leticia Cedillo-Barrón
Vaccination is one of the most effective prophylactic public health interventions for the prevention of infectious diseases such as coronavirus disease (COVID-19). Considering the ongoing need for new COVID-19 vaccines, it is crucial to modify our approach and incorporate more conserved regions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to effectively address emerging viral variants. The nucleocapsid protein is a structural protein of SARS-CoV-2 that is involved in replication and immune responses. Furthermore, this protein offers significant advantages owing to the minimal accumulation of mutations over time and the inclusion of key T-cell epitopes critical for SARS-CoV-2 immunity. A novel strategy that may be suitable for the new generation of vaccines against COVID-19 is to use a combination of antigens, including the spike and nucleocapsid proteins, to elicit robust humoral and potent cellular immune responses, along with long-lasting immunity. The strategic use of multiple antigens aims to enhance vaccine efficacy and broaden protection against viruses, including their variants. The immune response against the nucleocapsid protein from other coronavirus is long-lasting, and it can persist up to 11 years post-infection. Thus, the incorporation of nucleocapsids (N) into vaccine design adds an important dimension to vaccination efforts and holds promise for bolstering the ability to combat COVID-19 effectively. In this review, we summarize the preclinical studies that evaluated the use of the nucleocapsid protein as antigen. This study discusses the use of nucleocapsid alone and its combination with spike protein or other proteins of SARS-CoV-2.
{"title":"The Key to Increase Immunogenicity of Next-Generation COVID-19 Vaccines Lies in the Inclusion of the SARS-CoV-2 Nucleocapsid Protein","authors":"Noe Juvenal Mendoza-Ramírez, Julio García-Cordero, Gaurav Shrivastava, Leticia Cedillo-Barrón","doi":"10.1155/2024/9313267","DOIUrl":"https://doi.org/10.1155/2024/9313267","url":null,"abstract":"Vaccination is one of the most effective prophylactic public health interventions for the prevention of infectious diseases such as coronavirus disease (COVID-19). Considering the ongoing need for new COVID-19 vaccines, it is crucial to modify our approach and incorporate more conserved regions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to effectively address emerging viral variants. The nucleocapsid protein is a structural protein of SARS-CoV-2 that is involved in replication and immune responses. Furthermore, this protein offers significant advantages owing to the minimal accumulation of mutations over time and the inclusion of key T-cell epitopes critical for SARS-CoV-2 immunity. A novel strategy that may be suitable for the new generation of vaccines against COVID-19 is to use a combination of antigens, including the spike and nucleocapsid proteins, to elicit robust humoral and potent cellular immune responses, along with long-lasting immunity. The strategic use of multiple antigens aims to enhance vaccine efficacy and broaden protection against viruses, including their variants. The immune response against the nucleocapsid protein from other coronavirus is long-lasting, and it can persist up to 11 years post-infection. Thus, the incorporation of nucleocapsids (N) into vaccine design adds an important dimension to vaccination efforts and holds promise for bolstering the ability to combat COVID-19 effectively. In this review, we summarize the preclinical studies that evaluated the use of the nucleocapsid protein as antigen. This study discusses the use of nucleocapsid alone and its combination with spike protein or other proteins of SARS-CoV-2.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"130 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141170967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jesse P. M. Viana, Fernanda F. Costa, Tatielle G. Dias, Priscila M. Mendes, Gabriel B. Copeland, Willian S. Nascimento, Sofia S. N. Mendes, Isabella F. S. Figueiredo, Elizabeth S. Fernandes, Anamelia L. Bocca, Márcia C. G. Maciel
Sepsis treatment is a challenging condition due to its complexity, which involves host inflammatory responses to a severe and potentially fatal infection, associated with organ dysfunction. The aim of this study was to analyze the scientific literature on the immunomodulatory effects of glucans in a murine model of systemic infection induced by cecal ligation and puncture. This study comprises an integrative literature review based on systematic steps, with searches carried out in the PubMed, ScienceDirect, Scopus, Web of Science, and Embase databases. In most studies, the main type of glucan investigated was β-glucan, at 50 mg/kg, and a reduction of inflammatory responses was identified, minimizing the occurrence of tissue damage leading to increased animal survival. Based on the data obtained and discussed in this review, glucans represent a promising biotechnological alternative to modulate the immune response and could potentially be used in the clinical management of septic individuals.
败血症治疗因其复杂性而具有挑战性，它涉及宿主对严重且可能致命的感染的炎症反应，并伴有器官功能障碍。本研究旨在分析有关葡聚糖在通过盲肠结扎和穿刺诱导的小鼠全身感染模型中的免疫调节作用的科学文献。本研究包括基于系统步骤的综合文献综述，在 PubMed、ScienceDirect、Scopus、Web of Science 和 Embase 数据库中进行了检索。在大多数研究中，调查的主要葡聚糖类型是 β-葡聚糖，剂量为 50 毫克/千克，结果发现它能减轻炎症反应，最大限度地减少组织损伤的发生，从而提高动物的存活率。根据本综述所获得和讨论的数据，葡聚糖是一种很有前景的调节免疫反应的生物技术替代品，有可能用于败血症患者的临床治疗。
{"title":"Glucans: A Therapeutic Alternative for Sepsis Treatment","authors":"Jesse P. M. Viana, Fernanda F. Costa, Tatielle G. Dias, Priscila M. Mendes, Gabriel B. Copeland, Willian S. Nascimento, Sofia S. N. Mendes, Isabella F. S. Figueiredo, Elizabeth S. Fernandes, Anamelia L. Bocca, Márcia C. G. Maciel","doi":"10.1155/2024/6876247","DOIUrl":"https://doi.org/10.1155/2024/6876247","url":null,"abstract":"Sepsis treatment is a challenging condition due to its complexity, which involves host inflammatory responses to a severe and potentially fatal infection, associated with organ dysfunction. The aim of this study was to analyze the scientific literature on the immunomodulatory effects of glucans in a murine model of systemic infection induced by cecal ligation and puncture. This study comprises an integrative literature review based on systematic steps, with searches carried out in the PubMed, ScienceDirect, Scopus, Web of Science, and Embase databases. In most studies, the main type of glucan investigated was <i>β</i>-glucan, at 50 mg/kg, and a reduction of inflammatory responses was identified, minimizing the occurrence of tissue damage leading to increased animal survival. Based on the data obtained and discussed in this review, glucans represent a promising biotechnological alternative to modulate the immune response and could potentially be used in the clinical management of septic individuals.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"235 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141170608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yisi Tan, Yuting Huang, Linkai Guo, Linghang Zhou, Keke Zhu, Yuancong Li, Jin Tan
<i>Background and Objective</i>. Oral submucous fibrosis (OSF) is a progressive and irreversible disorder of collagen metabolism, resulting in mucosal fibrosis, oral functional changes, and even malignant transformation. This study investigated the relationship between human leukocyte antigen (HLA)-DQB1 alleles and the susceptibility to OSF in a Hunan Han population, providing a new basis for clinical prevention and treatment of OSF. <i>Methods</i>. 44 OSF patients and 44 healthy volunteers were included in this study. To detect the expression frequency of HLA-DQB1 alleles in the two groups and analyze significant allelic subtypes and their relative risk, polymerase chain reaction (PCR) sequence-specific primers were used. Subsequently, based on the identification of differential genes, we compare the gene expression levels of OSF patients and healthy volunteers expressing differential genes by real-time quantitative PCR. <i>Results</i>. The expression frequency of the HLA-DQB1<svg height="10.1524pt" style="vertical-align:-0.04990005pt" version="1.1" viewbox="-0.0498162 -10.1025 8.3578 10.1524" width="8.3578pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.0091,0,0,-0.0091,2.179,-5.741)"></path></g></svg>05 : 02 allele in the OSF group (36.4%) was significantly higher than in the controls (13.6%), and exposure to the HLA-DQB1<svg height="10.1524pt" style="vertical-align:-0.04990005pt" version="1.1" viewbox="-0.0498162 -10.1025 8.3578 10.1524" width="8.3578pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.0091,0,0,-0.0091,2.179,-5.741)"><use xlink:href="#g50-43"></use></g></svg>05 : 02 allele was strongly related to OSF (OR (95% CI) = 3.619 (1.257,10.421), Wald <i>χ</i><sup>2</sup> = 5.681, <span><svg height="8.8423pt" style="vertical-align:-0.2064009pt" version="1.1" viewbox="-0.0498162 -8.6359 19.289 8.8423" width="19.289pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"></path></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"></path></g></svg><span></span><span><svg height="8.8423pt" style="vertical-align:-0.2064009pt" version="1.1" viewbox="22.8711838 -8.6359 28.182 8.8423" width="28.182pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,22.921,0)"></path></g><g transform="matrix(.013,0,0,-0.013,29.161,0)"></path></g><g transform="matrix(.013,0,0,-0.013,32.125,0)"><use xlink:href="#g113-49"></use></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"></path></g><g transform="matrix(.013,0,0,-0.013,44.605,0)"></path></g></svg>).</span></span> However, there were no significant differences in the allele expression frequencies of DQB1<svg height="10.1524pt" style="vertical-align:-0.04990005pt" version="1.1" viewbox="-0.0498162 -10.1025 8.3578 10.1524" width="8.3578pt" xmlns="http://www.w3.org/2000/svg"
{"title":"HLA-DQB1 Allele Polymorphism Associated with Oral Submucous Fibrosis in Hunan, China","authors":"Yisi Tan, Yuting Huang, Linkai Guo, Linghang Zhou, Keke Zhu, Yuancong Li, Jin Tan","doi":"10.1155/2024/8757860","DOIUrl":"https://doi.org/10.1155/2024/8757860","url":null,"abstract":"<i>Background and Objective</i>. Oral submucous fibrosis (OSF) is a progressive and irreversible disorder of collagen metabolism, resulting in mucosal fibrosis, oral functional changes, and even malignant transformation. This study investigated the relationship between human leukocyte antigen (HLA)-DQB1 alleles and the susceptibility to OSF in a Hunan Han population, providing a new basis for clinical prevention and treatment of OSF. <i>Methods</i>. 44 OSF patients and 44 healthy volunteers were included in this study. To detect the expression frequency of HLA-DQB1 alleles in the two groups and analyze significant allelic subtypes and their relative risk, polymerase chain reaction (PCR) sequence-specific primers were used. Subsequently, based on the identification of differential genes, we compare the gene expression levels of OSF patients and healthy volunteers expressing differential genes by real-time quantitative PCR. <i>Results</i>. The expression frequency of the HLA-DQB1<svg height=\"10.1524pt\" style=\"vertical-align:-0.04990005pt\" version=\"1.1\" viewbox=\"-0.0498162 -10.1025 8.3578 10.1524\" width=\"8.3578pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.0091,0,0,-0.0091,2.179,-5.741)\"></path></g></svg>05 : 02 allele in the OSF group (36.4%) was significantly higher than in the controls (13.6%), and exposure to the HLA-DQB1<svg height=\"10.1524pt\" style=\"vertical-align:-0.04990005pt\" version=\"1.1\" viewbox=\"-0.0498162 -10.1025 8.3578 10.1524\" width=\"8.3578pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.0091,0,0,-0.0091,2.179,-5.741)\"><use xlink:href=\"#g50-43\"></use></g></svg>05 : 02 allele was strongly related to OSF (OR (95% CI) = 3.619 (1.257,10.421), Wald <i>χ</i><sup>2</sup> = 5.681, <span><svg height=\"8.8423pt\" style=\"vertical-align:-0.2064009pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.6359 19.289 8.8423\" width=\"19.289pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,0,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,11.658,0)\"></path></g></svg><span></span><span><svg height=\"8.8423pt\" style=\"vertical-align:-0.2064009pt\" version=\"1.1\" viewbox=\"22.8711838 -8.6359 28.182 8.8423\" width=\"28.182pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,22.921,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,29.161,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,32.125,0)\"><use xlink:href=\"#g113-49\"></use></g><g transform=\"matrix(.013,0,0,-0.013,38.365,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,44.605,0)\"></path></g></svg>).</span></span> However, there were no significant differences in the allele expression frequencies of DQB1<svg height=\"10.1524pt\" style=\"vertical-align:-0.04990005pt\" version=\"1.1\" viewbox=\"-0.0498162 -10.1025 8.3578 10.1524\" width=\"8.3578pt\" xmlns=\"http://www.w3.org/2000/svg\" ","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"36 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141060675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective. Immunotherapy has proven effective in treating advanced gastric cancer (AGC), yet its benefits are limited to a subset of patients. Our aim is to swiftly identify prognostic biomarkers using cytokines to improve the precision of clinical guidance and decision-making for PD-1 inhibitor-based cancer immunotherapy in AGC. Materials and Methods. The retrospective study compared 36 patients with AGC who received combined anti-PD-1 immunotherapy and chemotherapy (immunochemotherapy) with a control group of 20 patients who received chemotherapy alone. The concentrations of TNF-α, IL-1β, IL-2R, IL-6, IL-8, IL-10, and IL-17 in the serum were assessed using chemiluminescence immunoassay at three distinct time intervals following the commencement of immunochemotherapy. Results. When compared to controls, patients undergoing immunochemotherapy demonstrated a generalized rise in cytokine levels after the start of treatment. However, patients who benefited from immunochemotherapy showed a decrease in IL-6 or IL-8 concentrations throughout treatment (with varied trends observed for IL-1β, IL-2R, IL-10, IL-17, and TNF-α) was evident in patients benefiting from immunochemotherapy but not in those who did not benefit. Among these markers, the combination of IL-6, IL-8, and CEA showed optimal predictive performance for short-term efficacy of immunochemotherapy in AGC patients. Conclusion. Reductions in IL-6/IL-8 levels observed during immunochemotherapy correlated with increased responsiveness to treatment effectiveness. These easily accessible blood-based biomarkers are predictive and rapid and may play a crucial role in identifying individuals likely to derive benefits from PD-1 blockade immunotherapy.
{"title":"An On-Treatment Decreased Trend of Serum IL-6 and IL-8 as Predictive Markers Quickly Reflects Short-Term Efficacy of PD-1 Blockade Immunochemotherapy in Patients with Advanced Gastric Cancer","authors":"Jiameng Liu, Yufei Mao, Chaoming Mao, Deqiang Wang, Liyang Dong, Wei Zhu","doi":"10.1155/2024/3604935","DOIUrl":"https://doi.org/10.1155/2024/3604935","url":null,"abstract":"<i>Objective</i>. Immunotherapy has proven effective in treating advanced gastric cancer (AGC), yet its benefits are limited to a subset of patients. Our aim is to swiftly identify prognostic biomarkers using cytokines to improve the precision of clinical guidance and decision-making for PD-1 inhibitor-based cancer immunotherapy in AGC. <i>Materials and Methods</i>. The retrospective study compared 36 patients with AGC who received combined anti-PD-1 immunotherapy and chemotherapy (immunochemotherapy) with a control group of 20 patients who received chemotherapy alone. The concentrations of TNF-<i>α</i>, IL-1<i>β</i>, IL-2R, IL-6, IL-8, IL-10, and IL-17 in the serum were assessed using chemiluminescence immunoassay at three distinct time intervals following the commencement of immunochemotherapy. <i>Results</i>. When compared to controls, patients undergoing immunochemotherapy demonstrated a generalized rise in cytokine levels after the start of treatment. However, patients who benefited from immunochemotherapy showed a decrease in IL-6 or IL-8 concentrations throughout treatment (with varied trends observed for IL-1<i>β</i>, IL-2R, IL-10, IL-17, and TNF-<i>α</i>) was evident in patients benefiting from immunochemotherapy but not in those who did not benefit. Among these markers, the combination of IL-6, IL-8, and CEA showed optimal predictive performance for short-term efficacy of immunochemotherapy in AGC patients. <i>Conclusion</i>. Reductions in IL-6/IL-8 levels observed during immunochemotherapy correlated with increased responsiveness to treatment effectiveness. These easily accessible blood-based biomarkers are predictive and rapid and may play a crucial role in identifying individuals likely to derive benefits from PD-1 blockade immunotherapy.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"21 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140937651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yingying Chen, Hui Li, Lin Zhu, Quan Yang, Jie Zhou
β-Glucan is the main component of the cell wall of pathogen-associated molecular patterns (PAMPs) including various yeast, fungi, or certain bacteria. Previous reports demonstrated that β-glucan was widely investigated as a potent immunomodulators to stimulate innate and adaptive immune responses, which indicated that it could be recommended as an effective adjuvant in immunotherapy. However, the detailed effects of β-glucan on neonatal immunity are still largely unknown. Here, we found that β-glucan did not affect the frequencies and numbers of myeloid cells in the spleen and bone marrow from neonates. Functional assay revealed that β-glucan from neonates compromised the immunosuppressive function of immature myeloid cells, which were myeloid-derived suppressor cells (MDSCs). Flow cytometry or gene expression analysis revealed that β-glucan-derived polymorphonuclear (PMN)-MDSCs produced lower level of reactive oxygen species (ROS) and arginase-1 (Arg1) in neonatal mice. Furthermore, β-glucan administration significantly decreased the frequency and ROS level of PMN-MDSCs in vitro. These observations suggest that β-glucan facilitates the maturation of myeloid cells in early life, which may contribute to its beneficial effects against immune disorders later in life.
{"title":"β-Glucan Subverts the Function of Myeloid Cells in Neonates","authors":"Yingying Chen, Hui Li, Lin Zhu, Quan Yang, Jie Zhou","doi":"10.1155/2024/2765001","DOIUrl":"https://doi.org/10.1155/2024/2765001","url":null,"abstract":"<i>β</i>-Glucan is the main component of the cell wall of pathogen-associated molecular patterns (PAMPs) including various yeast, fungi, or certain bacteria. Previous reports demonstrated that <i>β</i>-glucan was widely investigated as a potent immunomodulators to stimulate innate and adaptive immune responses, which indicated that it could be recommended as an effective adjuvant in immunotherapy. However, the detailed effects of <i>β</i>-glucan on neonatal immunity are still largely unknown. Here, we found that <i>β</i>-glucan did not affect the frequencies and numbers of myeloid cells in the spleen and bone marrow from neonates. Functional assay revealed that <i>β</i>-glucan from neonates compromised the immunosuppressive function of immature myeloid cells, which were myeloid-derived suppressor cells (MDSCs). Flow cytometry or gene expression analysis revealed that <i>β</i>-glucan-derived polymorphonuclear (PMN)-MDSCs produced lower level of reactive oxygen species (ROS) and arginase-1 (<i>Arg1</i>) in neonatal mice. Furthermore, <i>β</i>-glucan administration significantly decreased the frequency and ROS level of PMN-MDSCs in vitro. These observations suggest that <i>β</i>-glucan facilitates the maturation of myeloid cells in early life, which may contribute to its beneficial effects against immune disorders later in life.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"136 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140937595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaoxiao Yu, Yating Gao, Xin Zhang, Longshan Ji, Miao Fang, Man Li, Yueqiu Gao
Hepatitis B virus (HBV) infection is a major global health issue and ranks among the top causes of liver cirrhosis and hepatocellular carcinoma. Although current antiviral medications, including nucleot(s)ide analogs and interferons, could inhibit the replication of HBV and alleviate the disease, HBV cannot be fully eradicated. The development of cellular and animal models for HBV infection plays an important role in exploring effective anti-HBV medicine. During the past decades, advancements in several cell culture systems, such as HepG2.2.15, HepAD38, HepaRG, hepatocyte-like cells, and primary human hepatocytes, have propelled the research in inhibiting HBV replication and expression and thus enriched our comprehension of the viral life cycle and enhancing antiviral drug evaluation efficacy. Mouse models, in particular, have emerged as the most extensively studied HBV animal models. Additionally, the present landscape of HBV therapeutics research now encompasses a comprehensive assessment of the virus’s life cycle, targeting numerous facets and employing a variety of immunomodulatory approaches, including entry inhibitors, strategies aimed at cccDNA, RNA interference technologies, toll-like receptor agonists, and, notably, traditional Chinese medicine (TCM). This review describes the attributes and limitations of existing HBV model systems and surveys novel advancements in HBV treatment modalities, which will offer deeper insights toward discovering potentially efficacious pharmaceutical interventions.
{"title":"Hepatitis B: Model Systems and Therapeutic Approaches","authors":"Xiaoxiao Yu, Yating Gao, Xin Zhang, Longshan Ji, Miao Fang, Man Li, Yueqiu Gao","doi":"10.1155/2024/4722047","DOIUrl":"https://doi.org/10.1155/2024/4722047","url":null,"abstract":"Hepatitis B virus (HBV) infection is a major global health issue and ranks among the top causes of liver cirrhosis and hepatocellular carcinoma. Although current antiviral medications, including nucleot(s)ide analogs and interferons, could inhibit the replication of HBV and alleviate the disease, HBV cannot be fully eradicated. The development of cellular and animal models for HBV infection plays an important role in exploring effective anti-HBV medicine. During the past decades, advancements in several cell culture systems, such as HepG2.2.15, HepAD38, HepaRG, hepatocyte-like cells, and primary human hepatocytes, have propelled the research in inhibiting HBV replication and expression and thus enriched our comprehension of the viral life cycle and enhancing antiviral drug evaluation efficacy. Mouse models, in particular, have emerged as the most extensively studied HBV animal models. Additionally, the present landscape of HBV therapeutics research now encompasses a comprehensive assessment of the virus’s life cycle, targeting numerous facets and employing a variety of immunomodulatory approaches, including entry inhibitors, strategies aimed at cccDNA, RNA interference technologies, toll-like receptor agonists, and, notably, traditional Chinese medicine (TCM). This review describes the attributes and limitations of existing HBV model systems and surveys novel advancements in HBV treatment modalities, which will offer deeper insights toward discovering potentially efficacious pharmaceutical interventions.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"8 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140885266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cintia Cevallos, Patricio Jarmoluk, Franco Sviercz, Cinthya A. M. López, Rosa N. Freiberger, M. Victoria Delpino, Jorge Quarleri
This study aims to explore the influence of coinfection with HCV and HIV on hepatic fibrosis. A coculture system was set up to actively replicate both viruses, incorporating CD4 T lymphocytes (Jurkat), hepatic stellate cells (LX-2), and hepatocytes (Huh7.5). LX-2 cells’ susceptibility to HIV infection was assessed through measurements of HIV receptor expression, exposure to cell-free virus, and cell-to-cell contact with HIV-infected Jurkat cells. The study evaluated profibrotic parameters, including programed cell death, ROS imbalance, cytokines (IL-6, TGF-β, and TNF-α), and extracellular matrix components (collagen, α-SMA, and MMP-9). The impact of HCV infection on LX-2/HIV-Jurkat was examined using soluble factors released from HCV-infected hepatocytes. Despite LX-2 cells being nonsusceptible to direct HIV infection, bystander effects were observed, leading to increased oxidative stress and dysregulated profibrotic cytokine release. Coculture with HIV-infected Jurkat cells intensified hepatic fibrosis, redox imbalance, expression of profibrotic cytokines, and extracellular matrix production. Conversely, HCV-infected Huh7.5 cells exhibited elevated profibrotic gene transcriptions but without measurable effects on the LX-2/HIV-Jurkat coculture. This study highlights how HIV-infected lymphocytes worsen hepatic fibrosis during HCV/HIV coinfection. They increase oxidative stress, profibrotic cytokine levels, and extracellular matrix production in hepatic stellate cells through direct contact and soluble factors. These insights offer valuable potential therapies for coinfected individuals.
本研究旨在探讨 HCV 和 HIV 共同感染对肝纤维化的影响。研究人员建立了一个可同时活跃复制两种病毒的共培养系统，其中包含 CD4 T 淋巴细胞（Jurkat）、肝星状细胞（LX-2）和肝细胞（Huh7.5）。LX-2 细胞对 HIV 感染的易感性是通过测量 HIV 受体表达、暴露于无细胞病毒以及与感染 HIV 的 Jurkat 细胞进行细胞间接触来评估的。研究评估了凋亡参数，包括程序性细胞死亡、ROS 失衡、细胞因子（IL-6、TGF-β 和 TNF-α）以及细胞外基质成分（胶原蛋白、α-SMA 和 MMP-9）。利用从感染 HCV 的肝细胞中释放的可溶性因子研究了 HCV 感染对 LX-2/HIV-Jurkat 的影响。尽管LX-2细胞不会直接感染HIV，但观察到了旁观者效应，导致氧化应激增加和凋亡细胞因子释放失调。与感染艾滋病毒的 Jurkat 细胞共培养会加剧肝纤维化、氧化还原失衡、凋亡细胞因子的表达和细胞外基质的生成。与此相反，HCV 感染的 Huh7.5 细胞表现出凋亡基因转录的升高，但对 LX-2/HIV-Jurkat 协同培养没有明显影响。这项研究强调了在 HCV/HIV 合并感染期间，HIV 感染的淋巴细胞是如何加剧肝纤维化的。它们通过直接接触和可溶性因子增加了肝星状细胞的氧化应激、促坏细胞因子水平和细胞外基质的产生。这些见解为双重感染者提供了宝贵的潜在疗法。
{"title":"Bystander Effects and Profibrotic Interactions in Hepatic Stellate Cells during HIV and HCV Coinfection","authors":"Cintia Cevallos, Patricio Jarmoluk, Franco Sviercz, Cinthya A. M. López, Rosa N. Freiberger, M. Victoria Delpino, Jorge Quarleri","doi":"10.1155/2024/6343757","DOIUrl":"https://doi.org/10.1155/2024/6343757","url":null,"abstract":"This study aims to explore the influence of coinfection with HCV and HIV on hepatic fibrosis. A coculture system was set up to actively replicate both viruses, incorporating CD4 T lymphocytes (Jurkat), hepatic stellate cells (LX-2), and hepatocytes (Huh7.5). LX-2 cells’ susceptibility to HIV infection was assessed through measurements of HIV receptor expression, exposure to cell-free virus, and cell-to-cell contact with HIV-infected Jurkat cells. The study evaluated profibrotic parameters, including programed cell death, ROS imbalance, cytokines (IL-6, TGF-<i>β</i>, and TNF-<i>α</i>), and extracellular matrix components (collagen, <i>α</i>-SMA, and MMP-9). The impact of HCV infection on LX-2/HIV-Jurkat was examined using soluble factors released from HCV-infected hepatocytes. Despite LX-2 cells being nonsusceptible to direct HIV infection, bystander effects were observed, leading to increased oxidative stress and dysregulated profibrotic cytokine release. Coculture with HIV-infected Jurkat cells intensified hepatic fibrosis, redox imbalance, expression of profibrotic cytokines, and extracellular matrix production. Conversely, HCV-infected Huh7.5 cells exhibited elevated profibrotic gene transcriptions but without measurable effects on the LX-2/HIV-Jurkat coculture. This study highlights how HIV-infected lymphocytes worsen hepatic fibrosis during HCV/HIV coinfection. They increase oxidative stress, profibrotic cytokine levels, and extracellular matrix production in hepatic stellate cells through direct contact and soluble factors. These insights offer valuable potential therapies for coinfected individuals.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"41 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140835024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Unlike T cells in other tissues, uterine T cells must balance strong immune defense against pathogens with tolerance to semiallogeneic fetus. Our previous study fully elucidated the characteristics of γδT cells in nonpregnant uterus and the mechanism modulated by estrogen. However, comprehensive knowledge of the immunological properties of αβT (including CD4+T cells and CD8+T) cells in nonpregnancy uterus has not been acquired. In this study, we fully compared the immunological properties of αβT cells between uterus and blood using mouse and human sample. It showed that most of CD4+T cells and CD8+T cells in murine uterus and human endometrium were tissue resident memory T cells which highly expressed tissue residence markers CD69 and/or CD103. In addition, both CD4+T cells and CD8+T cells in uterus highly expressed inhibitory molecular PD-1 and cytokine IFN-γ. Uterine CD4+T cells highly expressed IL-17 and modulated by transcription factor pSTAT3. Moreover, we compared the similarities and differences between human and murine uterine T cell phenotype. Together, uterine CD4+T cells and CD8+ cells exhibited a unique mixed signature of T cell dysfunction, activation, and effector function which enabled them to balance strong immune defense against pathogens with tolerance to fetus. Our study fully elucidated the unique immunologic properties of uterine CD4+T and CD8+T cells and provided a base for further investigation of functions.
{"title":"CD4+T and CD8+T Cells in Uterus Exhibit Both Selective Dysfunction and Residency Signatures","authors":"Shuangpeng Kang, Shuiping Jin, Xueying Mao, BinSheng He, Changyou Wu","doi":"10.1155/2024/5582151","DOIUrl":"https://doi.org/10.1155/2024/5582151","url":null,"abstract":"Unlike T cells in other tissues, uterine T cells must balance strong immune defense against pathogens with tolerance to semiallogeneic fetus. Our previous study fully elucidated the characteristics of <i>γδ</i>T cells in nonpregnant uterus and the mechanism modulated by estrogen. However, comprehensive knowledge of the immunological properties of <i>αβ</i>T (including CD4<sup>+</sup>T cells and CD8<sup>+</sup>T) cells in nonpregnancy uterus has not been acquired. In this study, we fully compared the immunological properties of <i>αβ</i>T cells between uterus and blood using mouse and human sample. It showed that most of CD4<sup>+</sup>T cells and CD8<sup>+</sup>T cells in murine uterus and human endometrium were tissue resident memory T cells which highly expressed tissue residence markers CD69 and/or CD103. In addition, both CD4<sup>+</sup>T cells and CD8<sup>+</sup>T cells in uterus highly expressed inhibitory molecular PD-1 and cytokine IFN-<i>γ</i>. Uterine CD4<sup>+</sup>T cells highly expressed IL-17 and modulated by transcription factor pSTAT3. Moreover, we compared the similarities and differences between human and murine uterine T cell phenotype. Together, uterine CD4<sup>+</sup>T cells and CD8<sup>+</sup> cells exhibited a unique mixed signature of T cell dysfunction, activation, and effector function which enabled them to balance strong immune defense against pathogens with tolerance to fetus. Our study fully elucidated the unique immunologic properties of uterine CD4<sup>+</sup>T and CD8<sup>+</sup>T cells and provided a base for further investigation of functions.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"10 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140634194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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