Human fused NKG2D–IL-15 protein controls xenografted human gastric cancer through the recruitment and activation of NK cells

Chen, Yan; Chen, Bei; Yang, Ti; Xiao, Weiming; Li, Qian; Ding, Yanbing; Ming-chun, JI; Ge, Xiaoqun; Gong, Weijuan

doi:10.1038/cmi.2015.81

Cited by 46 publications

(43 citation statements)

References 47 publications

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“…On day 16, all mice were sacrificed, and tumour tissues were collected. Mononuclear cells in tumours were isolated as performed previously . Macrophages in tumour tissues were detected by flow cytometry or histology.…”

Section: Methodsmentioning

confidence: 99%

Increased M1 macrophages in young miR‐15a/16^−/− mice with tumour grafts or dextran sulphate sodium‐induced colitis

Jia

Han

et al. 2018

Scand J Immunol

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M1 macrophages are involved in inflammation by producing proinflammatory cytokines, whereas M2 macrophages are associated with wound healing and tissue regeneration by producing anti-inflammatory cytokines. MicroRNAs are involved in macrophage polarization. To evaluate whether miR-15a/16 is involved in macrophage polarization under tumour or inflammation microenvironments, we observed the growth of transplanted hepatic cancer (H22) cells or severity of dextran sulphate sodium (DSS)-induced colitis in 8-week-old miR-15a/16 knockout (KO) mice. Compared with littermate controls, the miR-15a/16 mice exhibited retarded tumour growth and increased sensibility to DSS-induced colitis. Meanwhile, the M1 cell frequencies were higher in tumour tissues and inflamed colons of KO mice than of littermate controls. Macrophages with miR-15a/16 deletion revealed an enhanced NF-κB transcription under the physiological state and lipopolysaccharide (LPS) or high mobility group box 1 (HMGB1) stimulation. STAT3 expression was also significantly increased in miR-15a/16 macrophages under LPS or HMGB1 stimulation. The polarization of M1 macrophages can be associated with the coactivation of NF-κB and STAT3. Results indicated that miR-15a/16 deficiency in the macrophages directs M1 polarization for tumour suppression and proinflammation. Thus, miR-15a/16 deletion in macrophages holds a distinct biological significance from that of the microRNA deficiency in tumour cells.

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Section: Methodsmentioning

confidence: 99%

Increased M1 macrophages in young miR‐15a/16^−/− mice with tumour grafts or dextran sulphate sodium‐induced colitis

Jia

Han

et al. 2018

Scand J Immunol

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“…The safety of adoptive transfer of autologous or allogeneic NK cells has been proved; however, efficacy is limited by their poor proliferation and persistence in vivo and the increase in Tregs related to IL-2 administration (53). Administration of exogenous IL-15 has been shown to improve survival, in vivo persistence, and therapeutic efficacy without inducing the survival and expansion of Tregs (54,55). A human NKG2D-IL-15 fusion protein could efficiently bind to major histocompatibility complex class I polypeptide-related sequence + tumor cells and stimulated NK cell activity by transpresentation of IL-15, thus exhibiting higher control efficiency of the growth of xenografted human gastric cancer via the NK cell recruitment and activation (55).…”

Section: Cytokine-activated Nk Cells In Tumor Immunotherapymentioning

confidence: 99%

Targeting Natural Killer Cells for Tumor Immunotherapy

Zhang

Shi

2020

Front. Immunol.

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Natural killer (NK) cells are important innate cytotoxic lymphocytes with a rapid and efficient capacity to recognize and kill tumor cells. In recent years, adoptive transfer of autologous-or allogeneic-activated NK cells has become a promising cellular therapy for cancer. However, the therapeutic efficiency is encouraging in hematopoietic malignancies, but disappointing in solid tumors, for which the use of NK-cell-based therapies presents considerable challenges. It is difficult for NK cells to traffic to, and infiltrate into, tumor sites. NK cell function, phenotype, activation, and persistence are impaired by the tumor microenvironment, even leading to NK cell dysfunction or exhaustion. Many strategies focusing on improving NK cells' durable persistence, activation, and cytolytic activity, including activation with cytokines or analogs, have been attempted. Modifying them with chimeric antigen receptors further increases the targeting specificity of NK cells. Checkpoint blockades can relieve the exhausted state of NK cells. In this review, we discuss how the cytolytic and effector functions of NK cells are affected by the tumor microenvironment and summarize the various immunotherapeutic strategies based on NK cells. In particular, we discuss recent advances in overcoming the suppressive effect of the tumor microenvironment with the aim of enhancing the clinical outcome in solid tumors treated with NK-cell-based immunotherapy.

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“…IL-15 is a pleiotropic cytokine that belongs to the 4-a-helical bundle family of cytokines and acts via the attachment to the receptor complex comprising IL15Rα (CD215), IL2Rβ (CD122) and the common γ (CD132) chains [217]. IL-15 is involved in the control of development, homeostasis, and functions of T cells, NK cells and NK-T cells [218,219]. It is also a vital cytokine for the control of B cells, DCs, macrophages, and mast cell functions.…”

Section: Mesenchymal Stem Cell-derived Il-15mentioning

confidence: 99%

Immunological Aspects of the Tumor Microenvironment and Epithelial-Mesenchymal Transition in Gastric Carcinogenesis

Baj

Brzozowska

Forma

et al. 2020

IJMS

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Infection with Helicobacter pylori, a Gram-negative, microaerophilic pathogen often results in gastric cancer in a subset of affected individuals. This explains why H. pylori is the only bacterium classified as a class I carcinogen by the World Health Organization. Several studies have pinpointed mechanisms by which H. pylori alters signaling pathways in the host cell to cause diseases. In this article, the authors have reviewed 234 studies conducted over a span of 18 years (2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015)(2016)(2017)(2018)(2019)(2020). The studies investigated the various mechanisms associated with gastric cancer induction. For the past 1.5 years, researchers have discovered new mechanisms contributing to gastric cancer linked to H. pylori etiology. Alongside alteration of the host signaling pathways using oncogenic CagA pathways, H. pylori induce DNA damage in the host and alter the methylation of DNA as a means of perturbing downstream signaling. Also, with H. pylori, several pathways in the host cell are activated, resulting in epithelial-to-mesenchymal transition (EMT), together with the induction of cell proliferation and survival. Studies have shown that H. pylori enhances gastric carcinogenesis via a multifactorial approach. What is intriguing is that most of the targeted mechanisms and pathways appear common with various forms of cancer.EMT refers to the process by which the mesenchymal phenotype is acquired by epithelial cells (ECs) mainly via the reduction of their intracellular adhesions and proliferative capacity (Figure 1.) [47].

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Human fused NKG2D–IL-15 protein controls xenografted human gastric cancer through the recruitment and activation of NK cells

Cited by 46 publications

References 47 publications

Increased M1 macrophages in young miR‐15a/16^−/− mice with tumour grafts or dextran sulphate sodium‐induced colitis

Increased M1 macrophages in young miR‐15a/16^−/− mice with tumour grafts or dextran sulphate sodium‐induced colitis

Targeting Natural Killer Cells for Tumor Immunotherapy

Immunological Aspects of the Tumor Microenvironment and Epithelial-Mesenchymal Transition in Gastric Carcinogenesis

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Human fused NKG2D–IL-15 protein controls xenografted human gastric cancer through the recruitment and activation of NK cells

Cited by 46 publications

References 47 publications

Increased M1 macrophages in young miR‐15a/16−/− mice with tumour grafts or dextran sulphate sodium‐induced colitis

Increased M1 macrophages in young miR‐15a/16−/− mice with tumour grafts or dextran sulphate sodium‐induced colitis

Targeting Natural Killer Cells for Tumor Immunotherapy

Immunological Aspects of the Tumor Microenvironment and Epithelial-Mesenchymal Transition in Gastric Carcinogenesis

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Product

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Increased M1 macrophages in young miR‐15a/16^−/− mice with tumour grafts or dextran sulphate sodium‐induced colitis

Increased M1 macrophages in young miR‐15a/16^−/− mice with tumour grafts or dextran sulphate sodium‐induced colitis