Trends in Immunotherapy最新文献

{"title":"Eucalyptus citriodora extract regulates cutaneous homeostasis including immune dysregulation and skin barrier dysfunction via the modulation of peroxisome proliferator-activated receptor-delta (PPAR-delata) pathway","authors":"A. Aioi, Takuhiro Yamada","doi":"10.24294/TI.V3.I1.1130","DOIUrl":"https://doi.org/10.24294/TI.V3.I1.1130","url":null,"abstract":"Perturbation of cutaneous homeostasis including immune dysregulation and skin barrier dysfunction evokes skin disorders. In this study, we examined the effect of Eucalyptus citriodora (Euc-c) extract on cytokine production, cell proliferation and cell differentiation in HaCaT cells to elucidate its influence on cutaneous homeostasis. Euc-c suppressed significantly LPS-induced IL-6 and TNF-a-induced IL-8 production from HaCaT cells. Conversely IL-1ra production was significantly enhanced by Euc-c. The expressions of IVL, CERS3 and CERS4, keratinocyte differentiation markers, were upregulated to 3.1, 2.8 and 2.7-fold respectively by Euc-c treatment, compared to the control, while the proliferation was downregulated. The lipid contents in Euc-c-treated cells tended to increase, compared with non-treated cells. To explore the underlying mechanism of these effect, we next performed siRNA experiments against PPAR-b/d. Euc-c enhanced PPAR-b/d mRNA expression to 3.25-fold, while PPAR-b/d mRNA expression in transfected cells was suppressed. The expressions of IVL, CERS3 and CERS4 in transfected cells were suppressed to 1.48, 0.82 and 0.72-fold respectively, concomitant with suppression of PPAR-b/d mRNA expression. These results indicated that Euc-c exerts anti-inflammatory effects and regulates keratinocyte differentiation via the modulation of PPAR-b/d pathway. Therefore, the application of Euc-c is expected to exert beneficial effect on skin disorders evoked by perturbation of skin homeostasis.Key words: Eucalyptus citriodora, PPAR-b/d, inflammation, barrier function, cutaneous homeostasis","PeriodicalId":401129,"journal":{"name":"Trends in Immunotherapy","volume":"186 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134095063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CAR-T therapy is breakthrough for intractable autoimmune disease?","authors":"F. Furukawa","doi":"10.24294/TI.V3.I1.1125","DOIUrl":"https://doi.org/10.24294/TI.V3.I1.1125","url":null,"abstract":"The dramatic effects of checkpoint inhibitor therapy[1,2] and chimeric antigen receptor T (CAR-T) cell therapy[3,4,5] have attracted a great deal of global attention and have recapitulated the history of cancer treatment so far. The recent approval of two CAR-T therapies by US Food and Drug Administration marked a very significant development in cell-based cancer immunotherapy. This milestone was demonstrated by the effectiveness of eradicating hematologic cancers using CD19-specific CARs. The success spurred development of immune cell therapies for other cancers, especially solid tumors. With regard to CAR-T therapy for solid tumors, although the clinical effects are limited, some unexpected serious adverse events have been reported and there are still many problems. The generation of novel CAR constructs for these cancer types represents a major challenge in bringing the technology ‘from-bench-to-bedside‘. In the review of Santos and Bernal[6], they outlined some new technologies to equip CAR-T cells to enhance efficiency while decreasing toxicity of CAR-T therapies in solid tumors. Development research on safer and more effective CAR-T therapy for solid tumors is in progress and will improve the outcome of treatment for patients with refractory leukemia and cancer in the future. Furthermore, it was expected that this CAR-T method would be applied to intractable autoimmune diseases. In the recent article of Kansal R et al[7], CD19-targeted CAR-T therapy is reported to be highly promising for intractable systemic lupus erythematosus. They used murine lupus models such as in the (NZB × NZW) F1 and MRL lpr/lpr mouse. New Zealand (NZ) mouse and MRL lpr/lpr mouse are well known to be a B-lupus model and a T-lupus model, respectively. The clinical trials of anti-CD20 antibody for lupus failed because of the transient and incomplete B cell depletion. They reported that CD8+ T cells expressing CD19-targeted CARs persistently depleted CD19+ B cells, eliminated autoantibody production, reversed disease manifestations in target organs, and extended life spans in murine lupus models. For human application, there will be many issues to be solved, but at least it will lead to the elucidation of the pathogenesis of intractable autoimmune diseases. References","PeriodicalId":401129,"journal":{"name":"Trends in Immunotherapy","volume":"37 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133434161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The most viewed articles in Trends in Immunotherapy Vol. 1, 2017.","authors":"F. Furukawa","doi":"10.24294/TI.V2.I4.1112","DOIUrl":"https://doi.org/10.24294/TI.V2.I4.1112","url":null,"abstract":"","PeriodicalId":401129,"journal":{"name":"Trends in Immunotherapy","volume":"12 8","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114085842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discontinuing voriconazole induced no completely regression of multiple cutaneous squamous cell carcinoma in a hematopoietic stem cell transplant patient","authors":"Y. Hirakawa, A. Okuno, A. Tanabe, Mutsumi Okada, N. Anzai, Yuki Yamamoto, F. Furukawa","doi":"10.24294/TI.V2.I4.1079","DOIUrl":"https://doi.org/10.24294/TI.V2.I4.1079","url":null,"abstract":"Voriconazole is a universal anti-fungal prophylaxis, which is frequently taken to the patients after hematopoietic stem cell transplantation and solid organ transplantation. Voriconazole can cause phototoxicity, multiple erythema in sun-exposed areas may develop actinic keratosis and cutaneous squamous cell carcinoma (cSCC) while taking voriconazole. In North America and Europe, case reports of phototoxicity and aggressive cSCC in patients on voriconazole have been documented. Also 4 cases of voriconazole-associated cSCC have recently been reported in Japan. We describe a Japanese woman with multiple cSCC associated with recurrence of cSCC after discontinuing voriconazole. ","PeriodicalId":401129,"journal":{"name":"Trends in Immunotherapy","volume":"4 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128266672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peroxisome Proliferator-Activated Receptors (PPARs) Activation as Therapeutic Targets in Skin Inflammation","authors":"A. Aioi","doi":"10.24294/TI.V4.I2.1063","DOIUrl":"https://doi.org/10.24294/TI.V4.I2.1063","url":null,"abstract":"Peroxisome proliferator-activated receptors (PPARs) are fatty acid activated transcription factors that belong to the nuclear hormone receptor family. They are initially known as transcriptional regulators of lipid and glucose metabolism, although further evidence has also been accumulated for other functions. Due to the nature of all PPAR isotypes which are expressed and exert effects by regulating the functions of cell types residing and infiltrating in the skin, PPARs represent a major research target for the understanding and treatment of many skin diseases. Atopic dermatitis (AD) is a chronic and relapsing disease characterized by skin barrier dysfunction and immune dysregulation. Skin barrier disturbance is one of the exacerbation factors of AD, due to facile penetration of molecules such as antigens. From the aspect of immune dysregulation, innate and acquired immunity including cell proliferation, cell differentiation, and cytokine network are involved in the pathogenesis. In this review, the role of PPAR in AD and the possibility of its agonist for the treatment of AD are discussed.","PeriodicalId":401129,"journal":{"name":"Trends in Immunotherapy","volume":"3 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125420422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antinuclear antibodies in Nakajo-Nishimura syndrome. A bridge with research on refractory autoimmune diseases","authors":"F. Furukawa","doi":"10.24294/TI.V2.I3.1078","DOIUrl":"https://doi.org/10.24294/TI.V2.I3.1078","url":null,"abstract":"   Nakajo-Nishimura syndrome (NNS) is an autosomal, recessively inherited disorder, which has been reported by Japanese physicians. This disease is characterized by remittent fever, pernio-like skin rashes, nodular erythema-like skin eruptions and partial lipodystrophy. NNS is an immunoproteasome-associated autoinflammatory disorder caused by a mutation of the PSMB8 gene. In general, autoinflammatory diseases are not associated with autoantibody production because it is assumed that autoinflammatory disorders are caused by the dysfunction of innate immunity and/or the dysfunction of proteasomes that have been collectively designated as proteasome-associated autoinflammatory syndromes. Autoinflammatory diseases were originally defined as diseases in which autoantibodies and autoreactive T cells were not detected, without activation of antigen-specific adaptive immune system, unlike autoimmune diseases. However, in recent years, as we previously reported, cases with the appearance of autoantibodies have been reported, and the boundaries are becoming vague.   We herein discuss the relationship between ANA and autoinflammatory NNS. We collected 9 cases with NNS, in which 5 cases showed positive ANA or anti-dsDNA antibody during the course.   The autoantibodies in NNS is also expected due to abnormal production and response of IFNα, but detailed pathological conditions need to be elucidated by accumulation and examination of further cases in the future. In other words, NNS will become a bridge with research on refractory autoimmune diseases.","PeriodicalId":401129,"journal":{"name":"Trends in Immunotherapy","volume":"27 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114216354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Disease-Modifying Drugs against Skin Fibrosis of Systemic Sclerosis","authors":"M. Nishiguchi, Yuki Yamamoto, M. Jinnin","doi":"10.24294/TI.V4.I2.1050","DOIUrl":"https://doi.org/10.24294/TI.V4.I2.1050","url":null,"abstract":"Systemic sclerosis (SSc) or scleroderma is an autoimmune disorder characterized by tissue fibrosis of the skin and internal organs. The etiology of the skin fibrosis is thought to be thickened dermis due to uncontrolled excessive deposition of various extracellular matrix, mainly type I collagen.Systemic treatments with anti-inflammatory and cytotoxic immunosuppressive properties, such as corticosteroids and immunosuppressants, are usually considered for skin sclerosis of patients with SSc. However, their approach must be initiated at the early stage, before the fibrosis is completed, and the effects of the corticosteroids and immunosuppressants are known to be reduced in the late stages of the sclerosis. Furthermore, various significant adverse effects of these treatments must be considered.This paper discusses the present day understanding of therapeutic options using disease-modifying drugs against skin sclerosis of SSc patients and the possible mechanisms. ","PeriodicalId":401129,"journal":{"name":"Trends in Immunotherapy","volume":" 100","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"120829580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CAR-T Therapy for Solid Tumors: Development of New Strategies","authors":"M. Santos, S. Bernal","doi":"10.24294/TI.V2.I3.1064","DOIUrl":"https://doi.org/10.24294/TI.V2.I3.1064","url":null,"abstract":"The recent approval of two CAR-T therapies by US Food and Drug Administration (FDA) marks a very significant development in cell-based cancer immunotherapy. This milestone was demonstrated by the effectiveness of eradicating hematologic cancers using CD19-specific CARs. The success spurred development of immune cell therapies for other cancers, especially solid tumors. The generation of novel CAR constructs for these cancer types represents a major challenge in bringing the technology ‘from-bench-to-bedside‘.In this review, we outline some new technologies we have developed to equip CAR-T cells to enhance efficiency while decreasing toxicity of CAR-T therapies in solid tumors.","PeriodicalId":401129,"journal":{"name":"Trends in Immunotherapy","volume":"8 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132047990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunogenic cell death: Chemoimmunotherapy in the clinic","authors":"A. Bulbul","doi":"10.24294/TI.V2.I2.970","DOIUrl":"https://doi.org/10.24294/TI.V2.I2.970","url":null,"abstract":"Although cancer chemotherapy has historically been considered immune suppressive, we now understand that combining chemoimmunotherapy incites a mechanism called Immunogenic cell death. These mechanisms are now moving from concepts to the clinic. Recently dramatic advances in lung cancer treatment by combining chemotherapy with immunotherapy have led the way to this new frontier in cancer medicine. We will explain the mechanism behind ICD and how it will perhaps breathe a new life into chemotherapy use in cancer, not front and center but as a helpful hand to immunotherapy. ","PeriodicalId":401129,"journal":{"name":"Trends in Immunotherapy","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114521059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of a humanized anti-human IL-6 receptor monoclonal antibody on Nakajo-Nishimura syndrome","authors":"F. Furukawa","doi":"10.24294/TI.V2.I3.1051","DOIUrl":"https://doi.org/10.24294/TI.V2.I3.1051","url":null,"abstract":"Nakajo-Nishimura syndrome (NNS) is a very rare hereditary disorder that has its onset in infancy with pernio-like skin rashes, and is accompanied by remittent fever and nodular erythema-like skin eruptions. The treatment of NNS is still under groping. Recently we encountered a case that was treated by corticosteroid and a humanized anti-human IL-6 receptor monoclonal antibody. As a result, the fever and skin rash was not improved sufficiently, and clinical symptoms of fat atrophy and joint contracture were gradually progressing. We herein report the effects of these agents and discuss the possibilities of new treatment direction.","PeriodicalId":401129,"journal":{"name":"Trends in Immunotherapy","volume":"12 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123454158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}