Nicotine stimulated dendritic cells could achieve anti-tumor effects in mouse lung and liver cancer.
BACKGROUND
Our previous studies have revealed that nicotine-treated immature dendritic cells (imDCs) have anti-tumor effects in murine lymphoma models. The present study is to explore the preventive and therapeutic anti-tumor effects of nicotine-treated imDCs in murine lung and liver cancer.


METHODS
To address this objection, bone marrow-derived imDCs were firstly stimulated by nicotine in vitro and the expressions of CD80, CD86, CD40, CD11b, MHC class I and II were determined by flow cytometry. Then, DCs-dependent tumor-lysate-specific T cell proliferation, IL-12(p40+p70) secretion were determined by BrdU cell proliferation assay and enzyme-linked immunosorbent assay, respectively. The anti-tumor effects of such imDCs were further explored by intraperitoneal transfer against tumor challenge or implantation. By using kinase inhibitors, the mechanism of nicotine upregulating CD80 was finally explored by flow cytometry.


RESULTS
The results showed that: firstly, nicotine could upregulate the expressions of CD80, CD86, CD40,CD11b, MHC class I and II molecules in imDCs. Secondly, nicotine could promote imDCs-dependent T cell priming and IL-12 secretion. Most importantly, systemic transfer of ex vivo nicotine-stimulated imDCs, which enhanced CD80 expression through PI3K activation, could reveal preventive and effectively therapeutic effects on tumor development.


CONCLUSIONS
Ex vivo nicotine stimulation can significantly improve imDCs efficacy for adaptive therapy of cancer. Nicotine-treated imDCs might be considered as a potential candidate for therapeutic tumor immunotherapy for lung and liver cancer.
Gao
Feng Guang
FG
Department of Basic Medicine Science, Medical College, Xiamen University, Xiamen 361005, People's Republic of China. gfengguang@xmu.edu.cn
Li
Hai Tao
HT
Li
Zhi Jing
ZJ
Gu
Jian Ren
JR
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D018122:B7-1 Antigen / Q000235:genetics / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D007167:Immunotherapy / Q000379:methods*; D008113:Liver Neoplasms / Q000276:immunology / Q000628:therapy; D008175:Lung Neoplasms / Q000276:immunology / Q000628:therapy; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009538:Nicotine / Q000276:immunology* / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology; D015854:Up-Regulation
D015703:Antigens, CD; D018122:B7-1 Antigen; D009538:Nicotine