Archivum Immunologiae et Therapiae Experimentalis最新文献

{"title":"The Role of Gut Microbiota in Gastrointestinal Tract Cancers","authors":"Marta Grochowska,&nbsp;Karol Perlejewski,&nbsp;Tomasz Laskus,&nbsp;Marek Radkowski","doi":"10.1007/s00005-021-00641-6","DOIUrl":"10.1007/s00005-021-00641-6","url":null,"abstract":"<div><p>Disturbances in gastrointestinal (GI) microbiota could play a significant role in the development of GI cancers, but the underlying mechanisms remain largely unclear. While some bacteria seem to facilitate carcinogenesis, others appear to be protective. So far only one bacterium (<i>Helicobacter pylori</i>) has been classified by the International Agency for Cancer Research as carcinogenic in humans but many other are the subject of intense research. Most studies on the role of microbiota in GI tract oncogenesis focus on pancreatic and colorectal cancers with the following three species: <i>Helicobacter pylori, Escherichia coli</i>, and <i>Porphyromonas gingivalis</i> as likely causative factors. This review summarizes the role of bacteria in GI tract oncogenesis.</p></div>","PeriodicalId":8389,"journal":{"name":"Archivum Immunologiae et Therapiae Experimentalis","volume":"70 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2022-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00005-021-00641-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39760020","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":"Effects of Local Nasal Immunotherapy with FIP-fve Peptide and Denatured Tyrophagus putrescentiae for Storage Mite-Induced Airway Inflammation","authors":"Chung-Yang Yen,&nbsp;Ching-Hsiang Yu,&nbsp;Jaw-Ji Tsai,&nbsp;Hsiang-Kuang Tseng,&nbsp;En-Chih Liao","doi":"10.1007/s00005-022-00645-w","DOIUrl":"10.1007/s00005-022-00645-w","url":null,"abstract":"<div><p>Allergic diseases are affecting public health and have increased over the last decade. Sensitization to mite allergens is a considerable trigger for allergy development. Storage mite-<i>Tyrophagus putrescentiae</i> shows great significance of allergenic potential and clinical relevance. The fungal immunomodulatory peptide FIP-<i>fve</i> has been reported to possess immunomodulatory activity. We aimed to determine whether <i>T. putrescentiae</i>-induced sensitization and airway inflammation in mice could be downregulated by FIP-<i>fve</i> in conjunction with denatured <i>T. putrescentiae</i> (FIP-<i>fve</i> and DN-Tp)<i>.</i> Immune responses and physiologic variations in immunoglobulins, leukocyte subpopulations, cytokine productions, pulmonary function, lung pathology, cytokines in CD4⁺ and Treg cells were evaluated after local nasal immunotherapy (LNIT). After the LNIT with FIP-<i>fve</i> and DN-Tp<i>,</i> levels of specific IgE, IgG1, and IgG2a in the sera and IgA in the bronchoalveolar lavage fluid (BALF) were significantly reduced. Infiltrations of inflammatory leukocytes (eosinophils, neutrophils, and lymphocytes) in the airway decreased significantly. Production of proinflammatory cytokines (IL-5, IL-13, IL-17F and IL-23) and chemokine (IL-8) were significantly reduced, and Th1-cytokine (IL-12) increased in the airway BALF after LNIT. Pulmonary functions of Penh values were significantly decreased after the methacholine challenge, which resulted in a reduction of airway hypersensitivity after LNIT. Bronchus pathology showed a reduction of inflammatory cell infiltration and epithelium damage after LNIT. The IL-4⁺/CD4⁺ T cells could be downregulated and the IFN-γ⁺/CD4⁺ T cells upregulated. The Treg-related immunity of IL-10 and Foxp3 expressions in CD4⁺CD25⁺ cells were both upregulated after LNIT. In conclusion, LNIT with FIP-<i>fve</i> and DN-Tp had an anti-inflammatory effect on mite-induced airway inflammations and possesses potential as an immunomodulatory therapy agent for allergic airway diseases.</p></div>","PeriodicalId":8389,"journal":{"name":"Archivum Immunologiae et Therapiae Experimentalis","volume":"70 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2022-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39875293","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 Role of Immunoproteasomes in Tumor-Immune Cell Interactions in Melanoma and Colon Cancer","authors":"Hanna Leister,&nbsp;Felix F. Krause,&nbsp;Rouzbeh Mahdavi,&nbsp;Ulrich Steinhoff,&nbsp;Alexander Visekruna","doi":"10.1007/s00005-022-00644-x","DOIUrl":"10.1007/s00005-022-00644-x","url":null,"abstract":"<div><p>The participation of proteasomes in vital cellular and metabolic processes that are involved in tumor growth has made this protease complex an attractive target for cancer treatment. In contrast to ubiquitously available constitutive proteasome, the increased enzymatic activity of immunoproteasome is associated with tumor-infiltrating immune cells, such as antigen-presenting cells and T lymphocytes. In various tumors, an effective anti-tumor immunity is provided through generation of tumor-associated antigens by proteasomes, contributing crucially to cancer eradication by T lymphocytes. The knowledge regarding the role of immunoproteasomes in the communication between tumor cells and infiltrating immune cells is limited. Novel data suggest that the involvement of immunoproteasomes in tumorigenesis is more complex than previously thought. In the intestine, in which diverse signals from commensal bacteria and food can contribute to the onset of chronic inflammation and inflammation-driven cancer, immunoproteasomes exert tumorigenic properties by modulating the expression of pro-inflammatory factors. In contrast, in melanoma and non-small cell lung cancer, the immunoproteasome acts against cancer development by promoting an effective anti-tumor immunity. In this review, we highlight the potential of immunoproteasomes to either contribute to inflammatory signaling and tumor development, or to support anti-cancer immunity. Further, we discuss novel therapeutic options for cancer treatments that are associated with modulating the activity of immunoproteasomes in the tumor microenvironment.</p></div>","PeriodicalId":8389,"journal":{"name":"Archivum Immunologiae et Therapiae Experimentalis","volume":"70 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2022-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00005-022-00644-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39848385","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":"Rho Kinases in Embryonic Development and Stem Cell Research","authors":"Jianjian Shi,&nbsp;Lei Wei","doi":"10.1007/s00005-022-00642-z","DOIUrl":"10.1007/s00005-022-00642-z","url":null,"abstract":"<div><p>The Rho-associated coiled-coil containing kinases (ROCKs or Rho kinases) belong to the AGC (PKA/PKG/PKC) family of serine/threonine kinases and are major downstream effectors of small GTPase RhoA, a key regulator of actin-cytoskeleton reorganization. The ROCK family contains two members, ROCK1 and ROCK2, which share 65% overall identity and 92% identity in kinase domain. ROCK1 and ROCK2 were assumed to be functionally redundant, based largely on their major common activators, their high degree kinase domain homology, and study results from overexpression with kinase constructs or chemical inhibitors. ROCK signaling research has expanded to all areas of biology and medicine since its discovery in 1996. The rapid advance is befitting ROCK’s versatile functions in modulating various cell behavior, such as contraction, adhesion, migration, proliferation, polarity, cytokinesis, and differentiation. The rapid advance is noticeably driven by an extensive linking with clinical medicine, including cardiovascular abnormalities, aberrant immune responsive, and cancer development and metastasis. The rapid advance during the past decade is further powered by novel biotechnologies including CRISPR-Cas and single cell omics. Current consensus, derived mainly from gene targeting and RNA interference approaches, is that the two ROCK isoforms have overlapping and distinct cellular, physiological and pathophysiology roles. In this review, we present an overview of the milestone discoveries in ROCK research. We then focus on the current understanding of ROCK signaling in embryonic development, current research status using knockout and knockin mouse models, and stem cell research.</p></div>","PeriodicalId":8389,"journal":{"name":"Archivum Immunologiae et Therapiae Experimentalis","volume":"70 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2022-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00005-022-00642-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39832236","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":"Peroxiredoxins as Markers of Oxidative Stress in IgA Nephropathy, Membranous Nephropathy and Lupus Nephritis","authors":"Natalia Krata,&nbsp;Bartosz Foroncewicz,&nbsp;Radosław Zagożdżon,&nbsp;Barbara Moszczuk,&nbsp;Magdalena Zielenkiewicz,&nbsp;Leszek Pączek,&nbsp;Krzysztof Mucha","doi":"10.1007/s00005-021-00638-1","DOIUrl":"10.1007/s00005-021-00638-1","url":null,"abstract":"<div><p>IgA nephropathy (IgAN), membranous nephropathy (MN), and lupus nephritis (LN) represent important causes of chronic kidney disease. They belong to the immune-mediated glomerulonephritis (GNs), and have distinct pathogenesis, distinct clinical courses, and variable responses to treatment. Therefore, specific diagnostic procedures are necessary for more effective patient management. Recently, a role for oxidative stress has been proposed in various renal disorders. Thus, molecules related to oxidative stress, such as 2-Cys-peroxiredoxins (PRDXs), may represent plausible candidates for biomarkers in renal pathologies. The aim of this study was to assess whether there are differences between individual GNs and healthy controls in the context of PRDXs serum concentration. We enrolled 108 patients with biopsy-proven IgAN (47), MN (26), LN (35) and 30 healthy age- and sex-matched controls. The serum concentrations of PRDX 1–5 were measured with ELISA assays and correlated with demographic and clinical data. The PRDXs’ concentration varied depending on the GN type. We also observed an association of PRDXs with lower estimated glomerular filtration rates, complement, hemoglobin, and body mass index. Our study indicates that individual PRDX can play roles in pathophysiology of selected GNs and that their serum concentrations may become useful as a new supplementary diagnostic markers in IgAN, MN as well as LN. The results of this study open a new avenue for prospective research on PRDXs in renal diseases.</p></div>","PeriodicalId":8389,"journal":{"name":"Archivum Immunologiae et Therapiae Experimentalis","volume":"70 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2021-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00005-021-00638-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39607448","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":"Prospects for Development of Induced Pluripotent Stem Cell-Derived CAR-Targeted Immunotherapies","authors":"Roberta Mazza,&nbsp;John Maher","doi":"10.1007/s00005-021-00640-7","DOIUrl":"10.1007/s00005-021-00640-7","url":null,"abstract":"<div><p>Technologies required to generate induced pluripotent stem cells (iPSC) were first described 15 years ago, providing a strong impetus to the field of regenerative medicine. In parallel, immunotherapy has finally emerged as a clinically meaningful modality of cancer therapy. In particular, impressive efficacy has been achieved in patients with selected haematological malignancies using ex vivo expanded autologous T cells engineered to express chimeric antigen receptors (CARs). While solid tumours account for over 90% of human cancer, they currently are largely refractory to this therapeutic approach. Nonetheless, given the considerable innovation taking place worldwide in the CAR field, it is likely that effective solutions for common solid tumours will emerge in the near future. Such a development will create significant new challenges in the scalable delivery of these complex, costly and individualised therapies. CAR-engineered immune cell products that originate from iPSCs offer the potential to generate unlimited numbers of homogeneous, standardised cell products in which multiple defined gene modification events have been introduced to ensure safety, potency and reproducibility. Here, we review some of the emerging strategies in use to engineer CAR-expressing iPSC-derived drug products.</p></div>","PeriodicalId":8389,"journal":{"name":"Archivum Immunologiae et Therapiae Experimentalis","volume":"70 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2021-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00005-021-00640-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39717316","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":"AITE Celebrates Its 70th Year of Publication (1953–2022)","authors":"Hubert Krotkiewski,&nbsp;Michał Zimecki,&nbsp;Andrzej Górski","doi":"10.1007/s00005-021-00639-0","DOIUrl":"10.1007/s00005-021-00639-0","url":null,"abstract":"","PeriodicalId":8389,"journal":{"name":"Archivum Immunologiae et Therapiae Experimentalis","volume":"70 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2021-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48766080","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":"A Novel Human Recombinant Lactoferrin Inhibits Lung Adenocarcinoma Cell Growth and Migration with No Cytotoxic Effect on Normal Human Epithelial Cells","authors":"Paulina Olszewska,&nbsp;Barbara Pazdrak,&nbsp;Marian L. Kruzel","doi":"10.1007/s00005-021-00637-2","DOIUrl":"10.1007/s00005-021-00637-2","url":null,"abstract":"<div><p>Lung cancer remains the leading cause of cancer death worldwide. Despite the recent advances in cancer treatment, only a subset of patients responds to targeted and immune therapies, and many patients developing resistance after an initial response. Lactoferrin (Lf) is a natural glycoprotein with immunomodulatory and anticancer activities. We produced a novel recombinant human Lf (rhLf) that exhibits glycosylation profile compatible with the natural hLf for potential parenteral therapeutic applications. The aim of this study was to evaluate the anticancer effects of this novel rhLf in human lung adenocarcinoma cells and its mechanisms of action. The results showed a concentration-dependent inhibition of A549 cancer cell growth in response to rhLf. Treatment with 1 mg/ml of rhLf for 24 h and 72 h resulted in a significant inhibition of cancer cell growth by 32% and 25%, respectively. Moreover, rhLf increased fourfold the percentage of early and late apoptotic cells compared to the control. This effect was accompanied by increased levels of caspase-3 activity and cell cycle arrest at the S phase in rhLf-treated cancer cells. Furthermore, rhLf significantly attenuated A549 cell migration. Importantly, treatment of normal human bronchial epithelial (NHBE) cells with rhLf showed the cell viability and morphology comparable to the control. In contrast, chemotherapeutic etoposide induced cytotoxicity in NHBE cells and reduced the cell viability by 40%. These results demonstrate the selective anticancer effects of rhLf against lung adenocarcinoma cells without cytotoxicity on normal human cells. This study highlights a potential for clinical utility of this novel rhLf in patients with lung cancer.</p></div>","PeriodicalId":8389,"journal":{"name":"Archivum Immunologiae et Therapiae Experimentalis","volume":"69 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2021-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00005-021-00637-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39599963","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":"Immunology and Donor-Specific Antibodies in Corneal Transplantation","authors":"Joanna Major,&nbsp;Bartosz Foroncewicz,&nbsp;Jacek Paweł Szaflik,&nbsp;Krzysztof Mucha","doi":"10.1007/s00005-021-00636-3","DOIUrl":"10.1007/s00005-021-00636-3","url":null,"abstract":"<div><p>The first human corneal transplantation was performed in 1905 by Eduard Zirm in the Olomouc Eye Clinic, now Czech Republic. However, despite great advancements in microsurgical eye procedures, penetrating keratoplasty in high-risk patients (e.g., vascularized or inflamed corneal tissue, consecutive transplants) remains a challenge. The difficulty is mainly due to the risk of irreversible allograft rejection, as an ocular immune privilege in these patients is abolished and graft rejection is the main cause of corneal graft failure. Therefore, tailored immunosuppressive treatment based on immunological monitoring [e.g., donor-specific antibodies (DSA)] is considered one of the best strategies to prevent rejection in transplant recipients. Although there is indirect evidence on the mechanisms underlying antibody-mediated rejection, the impact of DSA on cornea transplantation remains unknown. Determining the role of pre-existing and/or de novo DSA could advance our understanding of corneal graft rejection mechanisms. This may help stratify the immunological risk of rejection, ultimately leading to personalized treatment for this group of transplant recipients.</p></div>","PeriodicalId":8389,"journal":{"name":"Archivum Immunologiae et Therapiae Experimentalis","volume":"69 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2021-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00005-021-00636-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39700380","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":"Molecular Genetics Diversity of Primary Hemophagocytic Lymphohistiocytosis among Polish Pediatric Patients","authors":"Katarzyna Bąbol-Pokora,&nbsp;Magdalena Wołowiec,&nbsp;Katarzyna Popko,&nbsp;Aleksandra Jaworowska,&nbsp;Yenan T. Bryceson,&nbsp;Bianca Tesi,&nbsp;Jan-Inge Henter,&nbsp;Wojciech Młynarski,&nbsp;Wanda Badowska,&nbsp;Walentyna Balwierz,&nbsp;Katarzyna Drabko,&nbsp;Krzysztof Kałwak,&nbsp;Lucyna Maciejka-Kembłowska,&nbsp;Anna Pieczonka,&nbsp;Grażyna Sobol-Milejska,&nbsp;Sylwia Kołtan,&nbsp;Iwona Malinowska,&nbsp;for the Polish Pediatric Hematology, Oncology Society","doi":"10.1007/s00005-021-00635-4","DOIUrl":"10.1007/s00005-021-00635-4","url":null,"abstract":"<div><p>Hemophagocytic lymphohistiocytosis (HLH) is a clinical syndrome of life-threatening inflammation caused by an excessive, prolonged and ineffective immune response. An increasing number of HLH cases is recognized in Poland, but the genetic causes of familial HLH (FHL) have not been reported. We investigated the molecular genetics and associated outcomes of pediatric patients who met HLH criteria. We studied 54 patients with HLH, 36 of whom received genetic studies. Twenty-five patients were subjected to direct sequencing of the <i>PRF1</i>, <i>UNC13D</i>, <i>STX11, XIAP</i> and <i>SH2D1A</i> genes. Additionally, 11 patients were subjected to targeted next-generation sequencing. In our study group, 17 patients (31%) were diagnosed with primary HLH, with bi-allelic FHL variants identified in 13 (36%) patients whereas hemizygous changes were identified in 4 patients with X-linked lymphoproliferative diseases. In addition, one patient was diagnosed with X-linked immunodeficiency with magnesium defect, Epstein–Barr virus infection and neoplasia due to a hemizygous <i>MAGT1</i> variant; another newborn was diagnosed with auto-inflammatory syndrome caused by <i>MVK</i> variants. The majority (65%) of FHL patients carried <i>UNC13D</i> pathogenic variants, whereas <i>PRF1</i> variants occurred in two patients. Novel variants in <i>UNC13D</i>, <i>PRF1</i> and <i>XIAP</i> were detected<i>.</i> Epstein–Barr virus was the most common trigger noted in 23 (65%) of the patients with secondary HLH. In three patients with secondary HLH, heterozygous variants of FHL genes were found. Overall survival for the entire study group was 74% with a median of 3.6 years of follow-up. Our results highlight the diversity of molecular causes of primary HLH in Poland.</p></div>","PeriodicalId":8389,"journal":{"name":"Archivum Immunologiae et Therapiae Experimentalis","volume":"69 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2021-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00005-021-00635-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39543003","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}