Interleukin-18-mediated interferon-gamma secretion is regulated by thymosin beta 4 in human NK cells

Lee, Ha‐Reum; Yoon, Sun Young; Song, Seung‐Wan; Park, Yoorim; Kim, Tae Sung; Kim, Seonghan; Hur, Dae Young; Song, Hyun Keun; Park, Hyun-Jeong; Cho, Daeho

doi:10.1016/j.imbio.2011.04.002

Cited by 15 publications

(12 citation statements)

References 51 publications

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“…IL-18 has shown to have anti-tumor effects in several murine tumor models when transferred into tumor cells, alone [12-14] or in combination with IL-12 [15] or IL-23 [16]. Similar with IL-12, IL-18 also has the ability to inhibit tumor angiogenesis and growth [17,18]. Moreover, combination of IL-12 and IL-18 can play an important role in progression and metastasis of gastric cancer [19].…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Cellular immunotherapy using irradiated lung cancer cell vaccine co-expressing GM-CSF and IL-18 can induce significant antitumor effects

et al. 2014

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BackgroundAlthough the whole tumor cell vaccine can provide the best source of immunizing antigens, there is still a limitation that most tumors are not naturally immunogenic. Tumor cells genetically modified to secrete immune activating cytokines have been proved to be more immunogenic. IL-18 could augment proliferation of T cells and cytotoxicity of NK cells. GM-CSF could stimulate dendritic cells, macrophages and enhance presentation of tumor antigens. In our study, we used mouse GM-CSF combined with IL-18 to modify Lewis lung cancer LL/2, then investigated whether vaccination could suppress tumor growth and promote survival.MethodsThe Lewis lung cancer LL/2 was transfected with co-expressing mouse GM-CSF and IL-18 plasmid by cationic liposome, then irradiated with a sublethal dose X ray (100 Gy) to prepare vaccines. Mice were subcutaneously immunized with this inactivated vaccine and then inoculated with autologous LL/2 to estimate the antitumor efficacy.ResultsThe studies reported here showed that LL/2 tumor cell vaccine modified by a co-expressing mouse GM-CSF and IL-18 plasmid could significantly inhibit tumor growth and increased survival of the mice bearing LL/2 tumor whether prophylactic or adoptive immunotherapy in vivo. A significant reduction of proliferation and increase of apoptosis were also observed in the tumor treated with vaccine of co-expressing GM-CSF and IL-18. The potent antitumor effect correlated with higher secretion levels of pro-inflammatory cytokines such as IL-18, GM-CSF, interferon-γ in serum, the proliferation of CD4+ IFN-γ+, CD8+ IFN-γ+ T lymphocytes in spleen and the infiltration of CD4+, CD8+ T in tumor. Furthermore, the mechanism of tumor-specific immune response was further proved by 51Cr cytotoxicity assay in vitro and depletion of CD4, CD8, NK immune cell subsets in vivo. The results suggested that the antitumor mechanism was mainly depended on CD4+, CD8+ T lymphocytes.ConclusionsThese results provide a new insight into therapeutic mechanisms of IL-18 plus GM-CSF modified tumor cell vaccine and provide a potential clinical cancer immunotherapeutic agent for improved antitumor immunity.

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Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Cellular immunotherapy using irradiated lung cancer cell vaccine co-expressing GM-CSF and IL-18 can induce significant antitumor effects

et al. 2014

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“…IGLL5 mutations were found only in the first two exons, outside the immunoglobulin‐like domain, and still need to be assessed for biological relevance. Due to its small size (44 amino acids), TMSB4X was easily found significantly mutated by MuSiC, and reports of its involvement in interferon γ (Lee et al, ) and Akt (Piao et al, ) signaling pathways offer several promising leads for future studies.…”

Section: Resultsmentioning

confidence: 99%

Whole exome sequencing of relapsed/refractory patients expands the repertoire of somatic mutations in diffuse large B‐cell lymphoma

Mareschal

Dubois

Viailly

et al. 2015

Genes Chromosomes & Cancer

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Despite the many efforts already spent to enumerate somatic mutations in diffuse large B-cell lymphoma (DLBCL), previous whole-genome and whole-exome studies conducted on patients of mixed outcomes failed at characterizing the 30% of patients who will relapse or resist current immunochemotherapies. To address this issue, we performed whole-exome sequencing of normal/tumoral DNA pairs in 14 relapsed/refractory (R/R) patients subclassified by full-transcriptome arrays (six activated B-cell like, three germinal center B-cell like, and five primary mediastinal B-cell lymphomas), from the LNH-03 LYSA clinical trial program. Aside from well-known DLBCL features, gene and pathway level recurrence analyses proposed several interesting leads including TBL1XR1 and activating mutations in IRF4 or in the insulin regulation pathway. Sequencing-based copy number analysis defined 23 short recurrently altered regions involving genes such as REL, CDKN2A, HYAL2, and TP53. Moreover, it highlighted mutations in genes such as GNA13, CARD11, MFHAS1, and PCLO as associated with secondary variant allele amplification events. The five primary mediastinal B-cell lymphomas (PMBL), while unexpected in a R/R cohort, showed a significantly higher mutation rate (P = 0.003) and provided many insights on this classical Hodgkin lymphoma related subtype. Novel genes such as XPO1, MFHAS1, and ITPKB were found particularly mutated, along with various cytokine-based signaling pathways. Among these analyses, somatic events in the NF-κB pathway were found preponderant in the three DLBCL subtypes, confirming its major implication in DLBCL aggressiveness and pinpointing several new candidate genes.

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“…Moreover, with advancing age defective erythropoiesis is also observed that can progress to anemia [79,80]. Here again, by releasing IL-1β and IL-18 from innate immunity cells, the Nlrp3 inflammasome may play a role, because, on the one hand, IL-1R signaling leads to a decrease in erythropoietin secretion in the kidney [81] and, on the other hand, IL-18 induces interferon gamma expression, which along with IL-1α synergistically inhibits erythroid colony formation [82].…”

Section: Involvement Of the Nlrp3 Inflammasome In The Inflammaging Ofmentioning

confidence: 99%

The Nlrp3 inflammasome as a “rising star” in studies of normal and malignant hematopoiesis

et al. 2020

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Recent investigations indicate that hematopoiesis is coregulated by innate immunity signals and by pathways characteristic of the activation of innate immunity cells that also operate in normal hematopoietic stem progenitor cells (HSPCs). This should not be surprising because of the common developmental origin of these cells from a hemato/lymphopoietic stem cell. An important integrating factor is the Nlrp3 inflammasome, which has emerged as a major sensor of changes in body microenvironments, cell activation, and cell metabolic activity. It is currently the best-studied member of the inflammasome family expressed in hematopoietic and lymphopoietic cells, including also HSPCs. It is proposed as playing a role in (i) the development and expansion of HSPCs, (ii) their release from bone marrow (BM) into peripheral blood (PB) in stress situations and during pharmacological mobilization, (iii) their homing to BM after transplantation, and (iv) their aging and the regulation of hematopoietic cell metabolism. The Nlrp3 inflammasome is also involved in certain hematological pathologies, including (i) myelodysplastic syndrome, (ii) myeloproliferative neoplasms, (iii) leukemia, and (iv) graft-versus-host disease (GvHD) after transplantation. The aim of this review is to shed more light on this intriguing intracellular protein complex that has become a "rising star" in studies focused on both normal steady-state and pathological hematopoiesis.

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Interleukin-18-mediated interferon-gamma secretion is regulated by thymosin beta 4 in human NK cells

Cited by 15 publications

References 51 publications

RETRACTED ARTICLE: Cellular immunotherapy using irradiated lung cancer cell vaccine co-expressing GM-CSF and IL-18 can induce significant antitumor effects

RETRACTED ARTICLE: Cellular immunotherapy using irradiated lung cancer cell vaccine co-expressing GM-CSF and IL-18 can induce significant antitumor effects

Whole exome sequencing of relapsed/refractory patients expands the repertoire of somatic mutations in diffuse large B‐cell lymphoma

The Nlrp3 inflammasome as a “rising star” in studies of normal and malignant hematopoiesis

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