期刊
ONCOTARGET
卷 7, 期 20, 页码 29620-29634出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.8813
关键词
TREM-2; lung cancer; IL-10; Syk; immunoregulation
资金
- National Natural Science Foundation of China [81170015, 81300009, 81472171]
- major project of Science Technology Department of Zhejiang Province, China [2012C13022-2]
- Zhejiang Provincial Natural Science Foundation of China [LY14H010002]
During infection, triggering receptor expressed on myeloid cells-2 (TREM-2) restrains dendritic cells (DCs) and macrophages (MFs) phagocytosis, as well as reduces pro-inflammatory cytokines release through DNAX-activation protein 12 (DAP12) signaling. However, the role of TREM-2 signaling in cancer has never been elucidated. In the current study, we found that TREM-2 was up-regulated on peripheral blood monocytes in tumor-bearing host. More TREM-2(+)DCs were detected in the lung of 3LL tumor-bearing mice. On the other hand, the level of TREM-2 on pulmonary MFs positively correlated with the pathological staging of lung cancer. However, surgical or chemotherapeutic reduction of tumor burden led to the obvious decline of TREM-2. In vitro, TREM-2 expression of bone marrow (BM)-derived DCs and MFs was induced by conditional medium (CM) containing the supernatant of 3LL cells. TREM-2(+)DCs from CM and/or tumor-bearing mice held altered phenotypes (CD80(Low)CD86(Low)MHCII(Low)) and impaired functions, such as, reduced interleukin (IL)-12 secretion, increased IL-10 production, and weakened ovalbumin (OVA)-endocytic capacity; also developed potent inhibitory effect on T cell proliferation that could be partially reversed by TREM-2 blockage. Moreover, spleen tyrosine kinase (Syk) inhibitor restrained IL-10 production of TREM-2(+)DC. Remarkably, IL-10 neutralizing antibody and Syk inhibitor both lowered the suppressive potential of TREM-2(+)DCs in T cell proliferation. Also, adoptive transfer of this TREM-2(+)DCs accelerated the tumor growth rather than jeopardized survival in lung cancer-bearing mice. In conclusion, these results indicate that TREM-2 might act as a negative immuno-regulatory molecule through Syk pathway in an IL-10 dependent manner and partially predicts prognosis in lung cancer patients.
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