| First Author | Qu J | Year | 2019 |
| Journal | Int J Cancer | Volume | 145 |
| Issue | 8 | Pages | 2225-2237 |
| PubMed ID | 31008530 | Mgi Jnum | J:289712 |
| Mgi Id | MGI:6434618 | Doi | 10.1002/ijc.32355 |
| Citation | Qu J, et al. (2019) CARD9 prevents lung cancer development by suppressing the expansion of myeloid-derived suppressor cells and IDO production. Int J Cancer 145(8):2225-2237 |
| abstractText | 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-kappaB) pathway was activated in CARD9(-/-) mice-derived MDSCs. Deficiency of CARD9 enhanced expression of indoleamine 2,3-dioxygenase (IDO) in MDSCs via noncanonical NF-kappaB 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-kappaB-IDO pathway in MDSCs which can inhibit the suppressive function of MDSCs and prevent lung cancer development. |
