CARD9 prevents lung cancer development by suppressing the expansion of myeloid‐derived suppressor cells and IDO production

Qu, Junxing; Liu, Ling; Xu, Qianyun; Ren, Jing; Xu, Zhen; Dou, Huan; Shen, Shihao; Hou, Yayi; Mou, Yongbin; Wang, Tingting

doi:10.1002/ijc.32355

Cited by 31 publications

(34 citation statements)

References 34 publications

(94 reference statements)

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“…Aberrant activation of CARD9 usually causes a series of inflammatory diseases or cancers. Qu et al demonstrated the critical role of CARD9 in the development of LC for the first time [38] and draw a conclusion that CARD9 prevented lung cancer development by suppressing the accumulation of immunosuppressive cells MDSCs and its downstream product IDO production. Moreover, correlations between CARD9 expressions and MDSCs relative genes were further confirmed in tumor tissues from…”

Section: Discussionmentioning

confidence: 99%

Ganoderma lucidum polysaccharide (GLP) enhances antitumor immune response by regulating differentiation and inhibition of MDSCs via a CARD9-NF-κB-IDO pathway

Wang

Fan

2020

Bioscience Reports

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A homogeneous polysaccharide (GLP), with an average molecular weight of 4.44 × 104 Da, was isolated and purified from the fruiting bodies of Ganoderma lucidum. In this work, we examined the antitumor activities of GLP using a mouse Lewis lung cancer (LLC) model and explored possible molecular pathways involved in its immunomodulatory mechanism on tumor–host interaction. GLP administration (25 and 100 mg/kg) significantly inhibited tumor growth, as evidenced by the decreased tumor volume and tumor weight, as well as histological features of tumor tissues with concomitant down-regulation of proliferating cell nuclear antigen (PCNA) proliferative marker. Less myeloid-derived suppressor cells (MDSCs) were accumulated in both spleen and tumor tissues from GLP-treated mice. In contrast, the percentage of CD4+ and CD8+ T cells together with the production of Th1-type cytokines (IFN-γ and IL-12) was increased in the spleen of LLC-bearing mice following GLP administration. Furthermore, GLP administration reversed the attenuated expression of CARD9, p-Syk and p-p65, and increased indoleamine 2,3-dioxygenase (IDO) protein expression in MDSCs of LLC-bearing mice. Collectively, our data demonstrated the first time that GLP induced the differentiation of MDSCs and inhibited the accumulation of MDSCs via CARD9-NF-κB-IDO pathway, thus prevented lung cancer development.

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Section: Discussionmentioning

confidence: 99%

Ganoderma lucidum polysaccharide (GLP) enhances antitumor immune response by regulating differentiation and inhibition of MDSCs via a CARD9-NF-κB-IDO pathway

Wang

Fan

2020

Bioscience Reports

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“…Further studies suggested that knocking down CARD9 expression enhanced the expression of IDO in MDSCs through the noncanonical NF-κB pathway, which manifested as increased expression of NIK, p-P100, p52, and RelB. Thus, the CARD9-NF-κB-IDO pathway in MDSCs can inhibit the suppressive function of MDSCs and prevent LC development [62].…”

Section: Caspase Recruitment Domain-containing Proteinmentioning

confidence: 99%

Myeloid-derived suppressor cells—new and exciting players in lung cancer

et al. 2020

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Lung cancer (LC) is the leading cause of cancer-related death worldwide due to its late diagnosis and poor outcomes. As has been found for other types of tumors, there is increasing evidence that myeloid-derived suppressor cells (MDSCs) play important roles in the promotion and progression of LC. Here, we briefly introduce the definition of MDSCs and their immunosuppressive functions. We next specifically discuss the multiple roles of MDSCs in the lung tumor microenvironment, including those in tumor growth and progression mediated by inhibiting antitumor immunity, and the associations of MDSCs with a poor prognosis and increased resistance to chemotherapy and immunotherapy. Finally, we also discuss preclinical and clinical treatment strategies targeting MDSCs, which may have the potential to enhance the efficacy of immunotherapy.

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“…In our opinion, for one thing, the expression of CARD9 varied in different NSCLC cells, a suggestion of important role of CARD9 within NSCLC cells for tumor development. For another, it is typical of tumor to accumulate myeloid cells [10], such as macrophages [12,20], which should lead to increased CARD9 in vivo. We surmised that dramatical downregulation of CARD9 in NSCLC cells contributed to the decreased CARD9 in vivo, which may play a role in NSCLC development.…”

Section: E C T O R C a R D 9 S H C O N T R O L S H C A R Dmentioning

confidence: 99%

“…Our previous research on the difference of protein profiles of the benign and malignant pleural effusion by proteomics technology found that CARD9 was decreased in malignant pleural effusion, and the mechanism was not clear [9]. In the latest study of CARD9 in lung cancer, Qu et al [10] reported that CARD9 suppressed lung cancer development by inhibiting the expansion of myeloid-derived suppressor cells (MDSCs) and indoleamine 2,3-dioxygenase (IDO) production.…”

Section: Introductionmentioning

confidence: 99%

Caspase Recruitment Domain Containing Protein 9 Suppresses Non-Small Cell Lung Cancer Proliferation and Invasion via Inhibiting MAPK/p38 Pathway

et al. 2020

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PurposeCaspase recruitment domain containing protein 9 (CARD9) has been demonstrated to be a pro-tumor factor in various cancers. However, our previous study found a significant decrease of CARD9 in malignant pleural effusion compared with benign pleural effusion. So we investigated the role of CARD9 in non-small cell lung cancer (NSCLC) and its working mechanism. Materials and MethodsImmunohistochemistry, western blot, and quantitative real-time polymerase chain reaction were used to detect the expression of CARD9 in specimens of NSCLC patients. The Cancer Genome Atlas (TCGA) databasewas also used to analyze the expression of CARD9 in NSCLC and its predicting value for prognosis. Immunofluorescence was used for CARD9 cellular location. Cell growth assay, clonal formation assay, wound healing assay, matrigel invasion assay, and flow cytometry were used to test cell proliferation, migration, invasion, apoptosis, and cycle progression of NSCLC cells with CARD9 knockdown or CARD9 overexpression. Co-immunoprecipitation was used to identify the interaction between CARD9 and B-cell lymphoma 10 (BCL10). SB203580 was used to inhibit p38 activation.ResultsCARD9 was decreased in NSCLC tissues compared with normal tissues; low CARD9 expression was associated with poor survival. CARD9 was expressed both in tumor cells and macrophages. Downregulation of CARD9 in NSCLC cells enhanced the abilities of proliferation, invasion and migration via activated MAPK/p38 signaling, while overexpression of CARD9 presented antitumor effects. BCL10 was identified to interact with CARD9.ConclusionWe demonstrate that CARD9 is an independent prognostic factor in NSCLC patients and inhibits proliferation, migration, and invasion by suppressing MAPK/p38 pathway in NSCLC cells.

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CARD9 prevents lung cancer development by suppressing the expansion of myeloid‐derived suppressor cells and IDO production

Cited by 31 publications

References 34 publications

Ganoderma lucidum polysaccharide (GLP) enhances antitumor immune response by regulating differentiation and inhibition of MDSCs via a CARD9-NF-κB-IDO pathway

Ganoderma lucidum polysaccharide (GLP) enhances antitumor immune response by regulating differentiation and inhibition of MDSCs via a CARD9-NF-κB-IDO pathway

Myeloid-derived suppressor cells—new and exciting players in lung cancer

Caspase Recruitment Domain Containing Protein 9 Suppresses Non-Small Cell Lung Cancer Proliferation and Invasion via Inhibiting MAPK/p38 Pathway

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