The Adaptor Protein CARD9 Protects against Colon Cancer by Restricting Mycobiota-Mediated Expansion of Myeloid-Derived Suppressor Cells

Wang, Tingting; Fan, Caibin; Yao, Anran; Xu, Xiaoxia; Zheng, Guoxing; You, Yun; Jiang, Changying; Zhao, Xihai; Hou, Yayi; Hung, Mien‐Chie; Lin, Xin

doi:10.1016/j.immuni.2018.08.018

Cited by 131 publications

(152 citation statements)

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“…demonstrate that CARD9 promotes sex‐biased colon tumors in the adenomatous polyposis coli multiple intestinal neoplasia (APC min ) mouse model. Our recently study on colitis‐associated colon cancer confirms a critical role of CARD9 in colon cancer . We found that CARD9 −/− mice are more susceptible to colitis‐associated cancer and outline a mechanism whereby fungal dysbiosis increases the frequency of MDSCs.…”

Section: Discussionsupporting

confidence: 70%

“…Our recently study on colitis-associated colon cancer confirms a critical role of CARD9 in colon cancer. 6 We found that CARD9 −/− mice are more susceptible to colitis-associated cancer and outline a mechanism whereby fungal dysbiosis increases the frequency of MDSCs. In our study, we found that supernatant from tumor cells can also differentiate MDSCs from BM cells, providing another regulatory way for MDSCs.…”

Section: Discussionmentioning

confidence: 76%

“…In addition, CARD9 also affects the macrophages polarization in a liver metastasis of colon carcinoma by NF‐κB pathways. Our recent study demonstrates a critical role of CARD9 in the development of colitis‐associated colon cancer . However, the detailed role of CARD9 in lung carcinoma remains unclear.…”

Section: Introductionmentioning

confidence: 96%

“…Our recent study demonstrates a critical role of CARD9 in the development of colitis-associated colon cancer. 6 However, the detailed role of CARD9 in lung carcinoma remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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

Liu

et al. 2019

Intl Journal of Cancer

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Caspase recruitment domain‐containing protein 9 (CARD9) is an adaptor protein and highly expressed in myeloid cells. Our previous study demonstrates a critical protective effect of CARD9 in the development of colitis‐associated colon cancer. Nevertheless, the effect of CARD9 in lung cancer remains unclear. Here, using a mouse Lewis lung cancer model, we found the tumor burden of CARD9−/− mice was much heavier than that in wild‐type (WT) mice. More myeloid‐derived suppressor cells (MDSCs) were accumulated and less cytotoxicity T lymphocyte was found in tumor tissues of CARD9−/− mice, compared to WT mice. Depleting MDSCs using anti‐Gr1 antibody can significantly decrease tumor burden in CARD9−/− mice. Furthermore, the noncanonical nuclear factor‐kappaB (NF‐κB) pathway was activated in CARD9−/− mice‐derived MDSCs. Deficiency of CARD9 enhanced expression of indoleamine 2,3‐dioxygenase (IDO) in MDSCs via noncanonical NF‐κB pathway. Moreover, correlations between CARD9 expressions and MDSCs relative genes (IDO, iNOS‐2 and arginase 1 [ARG‐1]) were further confirmed in tumor tissues from lung cancer patients. Taken together, we showed a CARD9‐NF‐κB‐IDO pathway in MDSCs which can inhibit the suppressive function of MDSCs and prevent lung cancer development.

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Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 76%

Section: Introductionmentioning

confidence: 96%

“…Our recent study demonstrates a critical role of CARD9 in the development of colitis-associated colon cancer. 6 However, the detailed role of CARD9 in lung carcinoma remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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

Liu

et al. 2019

Intl Journal of Cancer

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“…Like bacteria, fungi are a component of the microbiota at barrier surfaces in mammals, where emerging studies suggest they play an important role in shaping host immunity and tissue homeostasis (Belkaid and Harrison, 2017;Iliev and Leonardi, 2017). Alterations in intestinal fungal composition and dysbiosis have been associated with human inflammatory disorders, such as inflammatory bowel disease (IBD), colorectal cancer, and allergy (Sokol et al, 2017;Wypych and Marsland, 2018;Coker et al, 2019), in which mutations or deficiencies in fungal recognition receptors or downstream signaling pathways have been shown to substantially influence disease severity (Iliev et al, 2012;Wang et al, 2016Wang et al, , 2018Li et al, 2018;Malik et al, 2018). Nevertheless, how fungi interact with the mammalian host and the molecular mechanisms mediating fungal recognition and resultant host responses remains incompletely defined.…”

Section: Introductionmentioning

confidence: 99%

Modulation of the fungal mycobiome is regulated by the chitin-binding receptor FIBCD1

Møeller

Leonardi

Schlosser

et al. 2019

Journal of Experimental Medicine

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Host–microbiota interactions are critical in regulating mammalian health and disease. In addition to bacteria, parasites, and viruses, beneficial communities of fungi (the mycobiome) are important modulators of immune- and tissue-homeostasis. Chitin is a major component of the fungal cell wall, and fibrinogen C containing domain 1 (FIBCD1) is a chitin-binding protein; however, the role of this molecule in influencing host–mycobiome interactions in vivo has never been examined. Here, we identify direct binding of FIBCD1 to intestinal-derived fungi and demonstrate that epithelial-specific expression of FIBCD1 results in significantly reduced fungal colonization and amelioration of fungal-driven intestinal inflammation. Collectively, these results identify FIBCD1 as a previously unrecognized microbial pattern recognition receptor through which intestinal epithelial cells can recognize and control fungal colonization, limit fungal dysbiosis, and dampen intestinal inflammation.

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Role of the Gut Microbiota and Its Metabolites in Tumorigenesis or Development of Colorectal Cancer

Zhang

et al. 2023

Advanced Science

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Colorectal cancer (CRC) is the most common cancer of the digestive system with high mortality and morbidity rates. Gut microbiota is found in the intestines, especially the colorectum, and has structured crosstalk interactions with the host that affect several physiological processes. The gut microbiota include CRC‐promoting bacterial species, such as Fusobacterium nucleatum, Escherichia coli, and Bacteroides fragilis, and CRC‐protecting bacterial species, such as Clostridium butyricum, Streptococcus thermophilus, and Lacticaseibacillus paracasei, which along with other microorganisms, such as viruses and fungi, play critical roles in the development of CRC. Different bacterial features are identified in patients with early‐onset CRC, combined with different patterns between fecal and intratumoral microbiota. The gut microbiota may be beneficial in the diagnosis and treatment of CRC; some bacteria may serve as biomarkers while others as regulators of chemotherapy and immunotherapy. Furthermore, metabolites produced by the gut microbiota play essential roles in the crosstalk with CRC cells. Harmful metabolites include some primary bile acids and short‐chain fatty acids, whereas others, including ursodeoxycholic acid and butyrate, are beneficial and impede tumor development and progression. This review focuses on the gut microbiota and its metabolites, and their potential roles in the development, diagnosis, and treatment of CRC.

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The Adaptor Protein CARD9 Protects against Colon Cancer by Restricting Mycobiota-Mediated Expansion of Myeloid-Derived Suppressor Cells

Cited by 131 publications

References 60 publications

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

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

Modulation of the fungal mycobiome is regulated by the chitin-binding receptor FIBCD1

Role of the Gut Microbiota and Its Metabolites in Tumorigenesis or Development of Colorectal Cancer

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