期刊
INTERNATIONAL JOURNAL OF CANCER
卷 145, 期 8, 页码 2225-2237出版社
WILEY
DOI: 10.1002/ijc.32355
关键词
CARD9; MDSCs; noncanonical NF-kappa B; IDO; lung cancer
类别
资金
- Nanjing Medical Science and Technique Development Foundation [ZKX17033]
- National Natural Science Foundation of China [81572354, 81772542]
- Natural Science Foundation of Jiangsu Province in China [BK20161400]
- Six talent peaks project in Jiangsu Province [WSW-031]
- Fundamental Research Funds for the Central Universities [021414380437]
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-kappa B) pathway was activated in CARD9(-/-) mice-derived MDSCs. Deficiency of CARD9 enhanced expression of indoleamine 2,3-dioxygenase (IDO) in MDSCs via noncanonical NF-kappa B 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-kappa B-IDO pathway in MDSCs which can inhibit the suppressive function of MDSCs and prevent lung cancer development.
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