Enhanced frequency and potential mechanism of B regulatory cells in patients with lung cancer.
BACKGROUND
Regulatory T cells (Tregs) and B cells (Bregs) play an important role in the development of lung cancer. The present study aimed to investigate the phenotype of circulating Tregs and Bregs in patients with lung cancer and explore potential mechanism by which lung cancer cells act on the development of both.


METHODS
Patients with lung cancer (n = 268) and healthy donors (n = 65) were enrolled in the study. Frequencies of Tregs and Bregs were measured by flow cytometry with antibodies against CD4, CD25, CD127, CD45RA, CD19, CD24, CD27 and IL-10 before and after co-cultures. qRT-PCR was performed to evaluate the mRNA levels of RANTES, MIP-1α, TGF-β, IFN-γ and IL-4.


RESULTS
We found a lower frequency of Tregs and a higher frequency of Bregs in patients with lung cancer compared to healthy donors. Co-culture of lung cancer cells with peripheral blood mononuclear cells could polarize the lymphocyte phenotype in the similar pattern. Lipopolysaccharide (LPS)-stimulated lung cancer cells significantly modulated regulatory cell number and function in an in vitro model.


CONCLUSIONS
We provide initial evidence that frequencies of peripheral Tregs decreased or Bregs increased in patients with lung cancer, which may be modulated directly by lung cancer cells. It seems cancer cells per se plays a crucial role in the development of tumor immunity.
Department of Pulmonary Medicine, Zhongshan Hospital, Shanghai, China. doctorbb06@gmail.com.
Jiebai
J
Zhou
Biomedical Research Center, Zhongshan Hospital, Shanghai, China. minzh1234@163.com.|Fudan University Center for Clinical Bioinformatics, Shanghai, China. minzh1234@163.com.
Zhihui
Z
Min
Department of Pulmonary Medicine, Zhongshan Hospital, Shanghai, China. dingzhang0814@sina.com.
Ding
D
Zhang
Department of Biomedical Sciences, UCL, London, UK. william_95a@hotmail.com.
William
W
Wang
Sidra Medical and Research Centre, Doha, Qatar. fmarincola@sidra.org.
Francesco
F
Marincola
Department of Pulmonary Medicine, Zhongshan Hospital, Shanghai, China. xiangdong.wang@clintransmed.org.|Biomedical Research Center, Zhongshan Hospital, Shanghai, China. xiangdong.wang@clintransmed.org.|Fudan University Center for Clinical Bioinformatics, Shanghai, China. xiangdong.wang@clintransmed.org.
Xiangdong
X
Wang
D060151:B-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*; D045744:Cell Line, Tumor; D054405:Chemokine CCL3 / Q000378:metabolism; D018920:Coculture Techniques; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008175:Lung Neoplasms / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014019:Tissue Donors; D016212:Transforming Growth Factor beta / Q000378:metabolism
D054405:Chemokine CCL3; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D007371:Interferon-gamma