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CARD9 prevents lung cancer development by suppressing the expansion of myeloid‐derived suppressor cells and IDO production
Author(s) -
Qu Junxing,
Liu Ling,
Xu Qianyun,
Ren Jing,
Xu Zhen,
Dou Huan,
Shen Sunan,
Hou Yayi,
Mou Yongbin,
Wang Tingting
Publication year - 2019
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.32355
Subject(s) - cancer research , myeloid derived suppressor cell , lung cancer , cancer , suppressor , immunology , medicine , biology , pathology
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.