The Influence Of Leptin On Regulatory T Cells In Breast Cancer In Mice

Background and Objective: Breast cancer is a kind of hormone dependent tumor,the incidence of which increases year by year around the world and becomes one of the most main reasons for female death.Breast cancer is associated with multiple endocrine factors,such as insulin,estrogen,leptin and so on.Moreover,the body’s immune status in the microenvironment of breast cancer also plays an important role in breast cancer’s progress.When the body is in a state of immunosuppression,especially in the local tumor microenvironment,the proportion of suppressing T cell subgroup in disorder,that could form immunosuppression network,so as to protect the tumor from immune attack,lead to tumor growth,invasion and metastasis.Regulatory T cells(Tregs)play important roles in graft tolerance and immune pathology through inhibiting T cell proliferation and cytokine secretion,as a subpopulation of suppressor T cells,thereby inhibiting the body’s immune response so as to prevent the sustained inflammation attacking healthy tissues and maintain immune balance.However,leptin is mainly secreted by fat cells.It can promote cancer incidence,progression,invasion and metastasis.Tregs in the tumor microenviroment are thought to be one of the major suppressors of anti-tumor immunity.But it has not been reported whether leptin can promote the number or proportion of Treg in breast cancer or not.This study was to investigate the effect and biological significance of leptin on regulatory T cells in murine mammary carcinoma model,to clarify the influence of leptin on immunological mechanism related to breast cancer,providing the basis for breast cancer prevention and treatment.Methods: 4T1 breast cancer cells were cultured and murine mammary carcinoma models were established by injected 4T1 breast cancer cells.Then the cancer model(diameter of tumor size is 2mm)murines were randomly divided into control and experimental groups.The experimental group was treated with leptin,while the control group was treated with the same volume of normal saline(NS).The change of tumor size was detected during leptin treated.After one week treating,lymphocytes in peripheral blood,tumor draining lymph node and spleen were isolated using peripheral blood lymphocyte separation medium.And regulatory T cells in those samples were measured by flow cytometry so as to analyze the effect of leptin on regulatory T cells in murine mammary carcinoma model.At the same time,serum of each murine was collected and the content of transforming growth factor-beta 1(TGF-β1)was detected by ELISA.Results: Compared with NS group,the murine mammary carcinoma model group that treated with leptin grew faster.The higher the leptin was,the larger the tumor size was.The percentage of regulatory T cells in peripheral blood and spleen were markedly increased with the increase of the leptin concentration(P<0.05)while unconspicuous in tumor draining lymph node(P>0.05).The content of TGF-β1 in serum also was markedly increased with the increase of the leptin concentration(P<0.05).Conclusions: Leptin can promote the growth of breast cancer.It can upregulate the content of serum TGF-β1 and especially increasing cell number and percentage of regulatory T cells of peripheral blood and spleen in tumor microenvironment.Thus the anti-tumor immunity is suppressed and the tumor growth is promoted.