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

Abstract:

: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.

journal_name

Int J Cancer

authors

Qu J,Liu L,Xu Q,Ren J,Xu Z,Dou H,Shen S,Hou Y,Mou Y,Wang T

doi

10.1002/ijc.32355

subject

Has Abstract

pub_date

2019-10-15 00:00:00

pages

2225-2237

issue

8

eissn

0020-7136

issn

1097-0215

journal_volume

145

pub_type

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