Cytokine Therapy

Ohno, Masasuke; Natsume, Atsushi; Wakabayashi, Toshihiko

doi:10.1007/978-1-4614-3146-6_7

Cited by 12 publications

(6 citation statements)

References 46 publications

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“…Numerous aspects involving including antigenic stimulation signal, T cell microenvironment, cytokine productions, and T cell surface molecules [6-8] have been investigated. More recently, microRNAs (miRNA), which participate in immunological regulation, have attracted much attention [9].…”

Section: Introductionmentioning

confidence: 99%

Dynamically expressed microRNA-15b modulates the activities of CD8+ T lymphocytes in mice with Lewis lung carcinoma

et al. 2013

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BackgroundCD8+ T cells are key members of adaptive immunity against tumorigenesis. As subset of CD8+ T cells, effector T cells (Te) and memory T cells (Tm) have different biological activities. The former can kill tumor cells but come into apoptosis in a certain period and the latter is static with the ability of self-renewal. Previous studies showed that microRNAs (miRNA) played critical roles in regulating adaptive immunity. This study aimed to identify the different expression of miRNAs between Te and Tm cells in tumor-bearing mice and to sort out the target miRNAs which can be regulated to improve anti-tumor activities of CD8+ T cells.MethodsmiRNA expression profiling was performed on CD8+ Te and Tm cells from mice with Lewis lung carcinoma. Differentially expressed miRNA (miRNA-15b) was chosen and analyzed by qRT-PCR. Then, flow cytometry, ELISA, and CFSE kit were used to evaluate the biological effects of miRNA-15b on apoptosis, cytokine secretion, phenotype, and proliferation of CD8+ T cell. The possible downstream target genes of this miRNA were also analyzed.ResultsAnalysis of miRNA microarray and qRT-PCR showed that the level of miRNA-15b was higher in CD8+ Tm cells than in Te cells. Higher expression of miRNA-15b was observed in CD8+ T cells from tumor-bearing mice than those from healthy ones. Transfection of CD8+ T cells with miRNA-15b mimics could prevent T cells from apoptosis by inhibiting the translation of DEDD (Death Effector Domain-containing DNA binding protein). Moreover, ectopic miRNA-15b could inhibit the activation of CD8+ T cells (via repressing the production of IL-2 and IFN-γ and expression of CD69) and promote expression of CD44 through unknown pathways.ConclusionUp-regulation of miRNA-15b in tumor environment might negatively regulate anti-tumor immunity through inhibiting function of CD8+ T cells. miRNA-15b might be a potential therapeutic target for immunotherapy.

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Section: Introductionmentioning

confidence: 99%

Dynamically expressed microRNA-15b modulates the activities of CD8+ T lymphocytes in mice with Lewis lung carcinoma

et al. 2013

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“…Indeed, some previous reports from our and other laboratories have also indicated that reduction of tumor load per se is associated with an improved myelopoiesis [25–27,48–50]. As tumor growth and its inhibition are also associated with alteration in cytokine repertoire [20,25,27,47–49,51–53], the role of cytokine-dependent modulation of BMC survival and differentiation is not ruled out. This notion is supported by two lines of evidences: (1) our previous finding has shown that exposure of tumor cells to orlistat triggers a decline in production of IL-4 and IL-10 [20,47].…”

Section: Discussionmentioning

confidence: 93%

Myelopoietic Efficacy of Orlistat in Murine Hosts Bearing T Cell Lymphoma: Implication in Macrophage Differentiation and Activation

2013

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Orlistat, an inhibitor of fatty acid synthase (FASN), acts as an antitumor agent by blocking de novo fatty acid synthesis of tumor cells. Although, myelopoiesis also depends on de novo fatty acid synthesis, the effect of orlistat on differentiation of macrophages, which play a central role in host’s antitumor defence, remains unexplored in a tumor-bearing host. Therefore, the present investigation was undertaken to examine the effect of orlistat administration on macrophage differentiation in a T cell lymphoma bearing host. Administration of orlistat (240 mg/kg/day/mice) to tumor-bearing mice resulted in a decline of tumor load accompanied by an augmentation of bone marrow cellularity and survival of bone marrow cells (BMC). The expression of apoptosis regulatory caspase-3, Bax and Bcl2 was modulated in the BMC of orlistat-administered tumor-bearing mice. Orlistat administration also resulted in an increase in serum level of IFN-γ along with decreased TGF-β and IL-10. BMC of orlistat-administered tumor-bearing mice showed augmented differentiation into macrophages accompanied by enhanced expression of macrophage colony stimulating factor (M-CSF) and its receptor (M-CSFR). The macrophages differentiated from BMC of orlistat-administered mice showed characteristic features of M1 macrophage phenotype confirmed by expression of CD11c, TLR-2, generation of reactive oxygen species, phagocytosis, tumor cell cytotoxicity, production of IL-1,TNF-α and nitric oxide. These novel findings indicate that orlistat could be useful to support myelopoesis in a tumor-bearing host.

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“…3. Cytokine Therapy (Brunton et al 1992;Hardinger et al 2016;Drosos 2002;Ohno et al 2012;Biotechnolgy Forum n.d.;Santamaria 2013;Delves n.d.): Cytokines are soluble factors that act as a tool for communication between the immune system. They are responsible for immune homeostasis in the body.…”

Section: • Adoptive T-cell Therapymentioning

confidence: 99%

Immunotherapy: A Concept

Kulwal

Sawarkar

2020

Immunotherapy – A Novel Facet of Modern Therapeutics

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Immunotherapy has emerged as a promising therapeutic strategy to combat cancer, autoimmune diseases and infectious diseases in the last few two decades. Immunotherapy is a type of treatment which involves induction, enhancement, or suppression of the immune system. This modern approach has changed the paradigm and revolutionized the concept of modern therapeutics. The approach lies on understanding the molecular basis of the disease and making medicine personalized, accurate, and precise. The therapy relies on the host's immune system and can be broadly categorized as activation or suppression immunotherapies. Health authorities worldwide have accepted and acknowledged the significance of immunotherapy. As a result of this numerous therapeutic moieties based on immunotherapy have received regulatory approval and are being used in clinical practice. This chapter discusses a broad overview of the concept and principle of immunotherapy and its utility in a wide plethora of diseases.

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Cytokine Therapy

Cited by 12 publications

References 46 publications

Dynamically expressed microRNA-15b modulates the activities of CD8+ T lymphocytes in mice with Lewis lung carcinoma

Dynamically expressed microRNA-15b modulates the activities of CD8+ T lymphocytes in mice with Lewis lung carcinoma

Myelopoietic Efficacy of Orlistat in Murine Hosts Bearing T Cell Lymphoma: Implication in Macrophage Differentiation and Activation

Immunotherapy: A Concept

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