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Gene Therapy for Lung Cancer
Published in Kenneth L. Brigham, Gene Therapy for Diseases of the Lung, 2020
Choon Taek Lee, David P. Carbone
IL-7 is a bone marrow stromal cell-derived cytokine that stimulates pre B-cell expansion. IL-7 also functions as a growth factor for thymocytes and CD4+ and CD8+ T cells. IL-7 can enhance the antigen presentation indirectly by increasing expression of costimulatory cell adhesion molecules such as ICAM-1 and inhibit the production of immunosuppressive cytokines such as TGF-β (28). The production of IL-7 by retroviral transduction in fibrosarcomas can decrease tumorigenicity and induce protective immunity against unmodified tumor challenge, and IL-7 transduction of immunogenic tumors can cause the regression of established lung metastasis (29). A clinical trial of cytokine gene therapy with IL-7 is planned in lung cancer, but no preliminary results are available.
Effects of rhlL-7 on Leukocyte Subsets in Mice: Implications for Antitumor Activity
Published in Ronald H. Goldfarb, Theresa L. Whiteside, Tumor Immunology and Cancer Therapy, 2020
Kristin L. Komschlies, Timothy T. Back, Theresa A. Gregorio, M. Eilene Gruys, Giovanna Damia, Robert H. Wiltrout, Connie R. Faltynek
Interleukin 7 (IL-7) is a 25 kDa glycoprotein that was originally characterized as a product of a cloned murine bone marrow stromal cell line (1,2), and its mRNA has since been detected in the thymus and spleen (3). Human and murine recombinant IL-7 exhibit a 60% homology at the protein level with all of the six cysteine residues conserved (4). in vitro, IL-7 induces the proliferation of pro-B and pre-B lymphocytes (1,2) and affects the growth of both immature and mature cells of the T lymphocyte lineage (5–9). IL-7 also induces lymphokine-activated killer (LAK) activity from human peripheral blood leukocytes (9,10) and mouse splenocytes (11) in vitro. Further, IL-7 affects myeloid progenitor cells since splenic granulocyte-macrophage colony forming units (CFU-GM) and multipotential CFU (CFU-GEMM) are increased in mice treated with IL-7 (12,13), while total bone marrow CFU are decreased (13). Thus, the aims of these studies are to 1) determine whether the administration of recombinant human IL-7 (rhlL-7) to mice could alter the incidence or total number of various lymphoid subsets and 2) assess the effects of IL-7 against experimental metastases in mice.
Intraepithelial T cells: Specialized T cells at epithelial surfaces
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
In addition to strong and/or sustained TCR signals for γδ-lineage commitment, specific transcription factors promote and bias specific differentiation. In that aspect, mice deficient for the Wnt-induced β-catenin-controlled T-cell factor-1 showed drastic reduction in all TCRαβ+ subsets and also in the TCRγδ+ nIETs but not in TCRγδ+ splenocytes. Also, signals transduced through IL-7R play nonredundant roles during survival and expansion of T-cell progenitors and the rearrangement of the TCRγ locus. Consequently, IL-7-deficient (IL-7−/−) mice lack TCRγδ cells in all tissues.
RNA-Seq Analysis of Clinical Samples from TCGA Reveal Molecular Signatures for Ovarian Cancer
Published in Cancer Investigation, 2023
Rucha M. Wadapurkar, Aruna Sivaram, Renu Vyas
The last decade has seen several studies attempting to discover novel biomarkers (6). With the advancement of next generation sequencing technology, the amount of genomic data in the public domain has increased exponentially and many researchers are working towards analyzing them in an attempt to discover and develop novel diagnostic and prognostic biomarkers (7,8). In one such study, co-occurrence of mutations in IL-7R gene was discovered in high grade serous carcinoma patients (9). In a recent study, Hou et al., presented a panel of 10 genes showing differential expression signature in ovarian cancer patients by analyzing the relationship between ovarian cancer and immune metagenes (10). In another study, important genes and pathways correlating endometriosis and ovarian cancer were predicted (11). Though several studies are available wherein the databases have been used for prediction of novel biomarkers, these studies have found limited application in clinical settings as they focus on individual genes rather than the association between a group of genes and their products. Differential co-expression networks were studied for various types of cancers like chronic lymphocytic leukaemia (12), breast cancer (13) and ovarian cancer (14). Gov and Arga, in their study showed network comprising of 84 genes which were differentially co-expressed and co-regulated between healthy and ovarian cancer patients (15).
An immunologist’s guide to immunosenescence and its treatment
Published in Expert Review of Clinical Immunology, 2022
Calogero Caruso, Mattia Emanuela Ligotti, Giulia Accardi, Anna Aiello, Giuseppina Candore
However, a cautionary note must be added regarding the clinical use of certain classes of these drugs. As it is clear by reading the present review, most changes of the immune system observed in older people reflect on one side the thymic involution during puberty and the degree of residual thymic function in older age, and, on the other hand, the individual immunobiography. This might mean that changing older people immune system equilibrium to mimic that of the young one might be counterproductive, hence introducing iatrogenic pathology. So, this suggests that any treatment of immunosenescence should require personalized treatment [116]. Regarding IL-7, then, available data suggest that IL-7 may have therapeutic potential in improving outcomes in situations requiring enhanced immunological responses [39]. However, this is more difficult to occur during the aging process since the integrity of the cortical and medullary thymic architecture and the presence of functional thymic epithelial cells are necessary to support and maintain thymopoiesis [153]. Thus, the effect of IL-7 on T cell development should probably require the prior restoration of thymic architecture.
Interaction of Interleukin 7 Receptor (IL7R) and IL6 Gene Polymorphisms with Smoking Associated with Susceptibility to Asthma in Chinese Han Adults
Published in Immunological Investigations, 2022
Jun-Wei Du, Ze-Lan Xu, Qin-Xing Xu
Asthma is characterized by chronic lower airway inflammation, airway hyperresponsiveness, and airway wall remodeling. According to the latest survey, there are approximately 300 million asthmatic patients worldwide, and the incidence and mortality rates of asthma have been steadily increasing in recent years (Masoli et al. 2004). Therefore, the disease has become a major public health problem affecting human health worldwide (Jaakkola and Jaakkola 2012). Asthma is a common and complicated disease that is influenced by many factors (Cook and Saglani 2016). Previous studies have reported that several complex and diverse risk factors, such as environment, immunity, lifestyle, and psychology, are closely related to the occurrence and development of asthma (Demirdag and Ramadan 2016; Hovland et al. 2015; Toskala and Kennedy 2015). Interleukin (IL) genes encode cytokines (Zheng et al. 2017; Zhou et al. 2018), which play an important role in chronic inflammatory processes in patients with asthma (Doshi et al. 2002). Several single nucleotide polymorphisms (SNPs) of IL genes have been reported previously, including IL6 (Tavakol et al. 2014) and IL7 receptor (IL7R) (Jo et al. 2004). The function of IL7 is mediated by its receptor, IL7R, which is a heterodimer protein and assists in the signal transduction of IL7. IL6 is secreted by monocytes/macrophages, T and B cells, and is also produced by primary pulmonary epithelial cells stimulated by various allergens (Turner et al. 2014; Zhu et al. 2010).