A correlation analysis of the changes in plasma level of transforming growth factor beta1 and lymphocyte subset percentages after radiotherapy for patients with lung cancer
Luo Jing,Wei Tingting,Xu Kunpeng,Xu Liming,Gong Linlin,Ren Kai,Wang Xin,Zhao Lujun
Department of Radiation Oncology,Tianjin Medical University Cancer Institute and Hospital,Key Laboratory of Cancer Prevention and Therapy,National Clinical Research Center for Cancer,Tianjin′s Clinical Research Center for Cancer,Tianjin 300060,China
Abstract：Objective To investigate the relationship between the change in plasma level of transforming growth factor-beta1(TGF-β1) after radiotherapy (RT) and short-term treatment outcomes in patients with lung cancer, and to analyze its relationship with the changes in lymphocyte subset percentages in peripheral blood. Methods In a prospective study, blood samples before, during, and after treatment were collected from 39 patients with lung cancer who were treated in our hospital from 2014 to 2016. Plasma level of TGF-β1 was measured by enzyme-linked immunosorbent assay. The percentages of lymphocyte subsets in peripheral blood were determined at each time point. At one month after RT, chest computed tomography was performed to evaluate the short-term treatment outcomes. The response evaluation criteria in solid tumors were used to determine whether there was any response or not. Results Patients with lower plasma levels of TGF-β1 after RT had significantly better short-term treatment outcomes (P<0.05). The changes in plasma level of TGF-β1 after 2 and 4 weeks of RT and at the end of RT were correlated to the changes in the percentages of CD4(+) T and CD8(+) T cells and the CD4(+)/CD8(+) ratio at the same time point (r=-0.581,-0.516,-0.648, P<0.001;r=0.558, 0.545, 0.626, P<0.001;r=-0.615,-0.648,-0.598, P<0.001). Conclusions Lung cancer patients with reduced TGF-β1 levels after RT have better treatment outcomes than those without decreases in TGF-β1 levels after RT. The mechanism may be related to anti-tumor immunity.
Luo Jing,Wei Tingting,Xu Kunpeng et al. A correlation analysis of the changes in plasma level of transforming growth factor beta1 and lymphocyte subset percentages after radiotherapy for patients with lung cancer[J]. Chinese Journal of Radiation Oncology, 2017, 26(2): 150-154.
[1] Kawakami Y.Cancer immunotherapy by immuno-checkpoint blockade[J].Rinsho Ketsueki,2015,56(10):2186-2194.DOI:10.11406/rinketsu.56.2186. [2] Hossain DM,Panda AK,Chakrabarty S,et al. MEK inhibition prevents tumour-shed transforming growth factor-beta-induced T-regulatory cell augmentation in tumour milieu[J].Immunology,2015,144(4):561-573.DOI:10.1111/imm.12397. [3] Fahmi T,Esendagli G,Yilmaz G,et al. Immune compartmentalization of T cell subsets in chemically-induced breast cancer[J].Scand J Immunol,2010,72(4):339-348.DOI:10.1111/j.1365-3083.2010.02447.x. [4] Yoshimura K,Laird LS,Chia CY,et al. Live attenuated Listeria monocytogenes effectively treats hepatic colorectal cancer metastases and is strongly enhanced by depletion of regulatory T cells[J].Cancer Res,2007,67(20):10058-10066.DOI:10.1158/0008-5472.CAN-07-0573. [5] Lin RL,Zhao LJ.Mechanistic basis and clinical relevance of the role of transforming growth factor-beta in cancer[J].Cancer Biol Med,2015,12(4):385-393.DOI:10.7497/j.issn.2095-3941.2015.0015. [6] Zhao L,Ji W,Zhang L,et al. Changes of circulating transforming growth factor-beta1 level during radiation therapy are correlated with the prognosis of locally advanced non-small cell lung cancer[J].J Thorac Oncol,2010;5(4):521-525.DOI:10.1097/JTO.0b013e3181cbf761. [7] Young KH,Newell P,Cottam B,et al. TGFbeta inhibition prior to hypofractionated radiation enhances efficacy in preclinical models[J].Cancer Immunol Res,2014,2(10):1011-1022.DOI:10.1158/2326-6066.CIR-13-0207. [8] Jakubowska K,Naumnik W,Niklinska W,Chyczewska E.Clinical Significance of HMGB-1 and TGF-beta Level in Serum and BALF of Advanced Non-Small Cell Lung Cancer[J].Adv Exp Med Biol,2015,852(3):49-58.DOI:10.1007/5584_2015_115. [9] Liu Y,Yu H,Zhang C,et al. Protective effects of berberine on radiation-induced lung injury via intercellular adhesion molecular-1 and transforming growth factor-beta-1 in patients with lung cancer[J].Eur J Cancer,2008,44(16):2425-2432.DOI:10.1016/j.ejca.2008.07.040. [10] Huang AL,Liu SG,Qi WJ,et al. TGF-beta1 protein expression in non-small cell lung cancers is correlated with prognosis[J].Asian Pac J Cancer Prev,2014,15(19):8143-8147.DOI:http://dx.doi.org/10.7314/APJCP.2014.15.19.8143. [11] Hjortkjaer M,Waldstrom M,Jakobsen A,et al. The prognostic value of BRCA1 and PARP expression in epithelial ovarian carcinoma:immunohistochemical detection[J].Int J Gynecol Pathol,2016.DOI:10.1097/PGP.0000000000000310. [12] Kumar S,Guleria R,Mohan A,et al. Efficacy of plasma TGF-beta1 level in predicting therapeutic efficacy and prognosis in patients with advanced non-small cell lung cancer[J].Cancer Invest,2011,29(3):202-207.DOI:10.3109/07357907.2010.543208. [13] Ke X,Zhang S,Xu J,et al. Non-small-cell lung cancer-induced immunosuppression by increased human regulatory T cells via Foxp3 promoter demethylation[J].Cancer Immunol Immunother,2016,65(5):587-599.DOI:10.1007/s00262-016-1825-6. [14] Mori A,Deola S,Xumerle L,et al. Next generation sequencing:new tools in immunology and hematology[J].Blood Res,2013,48(4):242-249.DOI:10.5045/br.2013.48.4.242. [15] Banat GA,Tretyn A,Pullamsetti SS,et al. Immune and inflammatory cell composition of human lung cancer stroma[J].PLoS One,2015,10(9):e0139073.DOI:10.1371/journal.pone.0139073. [16] Hanahan D,Weinberg RA.Hallmarks of cancer:the next generation[J].Cell,2011,144(5):646-674.DOI:10.1016/j.cell.2011.02.013. [17] Schaue D,Xie MW,Ratikan JA,McBride WH.Regulatory T cells in radiotherapeutic responses[J].Front Oncol,2012,2:90.DOI:10.3389/fonc.2012.00090. [18] Schmidt A,Eriksson M,Shang MM,et al. Comparative analysis of protocols to induce human CD4+Foxp3+ regulatory T cells by combinations of IL-2,TGF-beta,retinoic acid,rapamycin and butyrate[J].PLoS One,2016,11(2):e0148474.DOI:10.1371/journal.pone.0148474. [19] Mohammed J,Beura LK,Bobr A,et al. Stromal cells control the epithelial residence of DCs and memory T cells by regulated activation of TGF-beta[J].Nat Immunol,2016,17(4):414-421.DOI:10.1038/ni.3396. [20] Sakaguchi S,Miyara M,Costantino CM,et al. FOXP3+ regulatory T cells in the human immune system[J].Nat Rev Immunol,2010,10(7):490-500.DOI:10.1038/nri2785. [21] Wilson S,Levy D.A mathematical model of the enhancement of tumor vaccine efficacy by immunotherapy[J].Bull Math Biol,2012,74(7):1485-1500.DOI:10.1007/s11538-012-9722-4. [22] Strauss L,Bergmann C,Szczepanski M,et al. A unique subset of CD4+CD25 highFoxp3+ T cells secreting interleukin-10 and transforming growth factor-beta1 mediates suppression in the tumor microenvironment[J].Clin Cancer Res,2007,13(15 Pt 1):4345-4354.DOI:10.1158/1078-0432.CCR-07-0472. [23] Hald SM,Bremnes RM,Al-Shibli K,et al. CD4/CD8 co-expression shows independent prognostic impact in resected non-small cell lung cancer patients treated with adjuvant radiotherapy[J].Lung Cancer,2013,80(2):209-215.DOI:10.1016/j.lungcan.2012.12.026. [24] Castriconi R,Cantoni C,Della Chiesa M,et al. Transforming growth factor beta 1 inhibits expression of NKp30 and NKG2D receptors:consequences for the NK-mediated killing of dendritic cells[J].Proc Natl Acad Sci USA,2003,100(7):4120-4125.DOI:10.1073/pnas.0730640100. [25] Ghiringhelli F,Menard C,Terme M,et al. CD4+CD25+ regulatory T cells inhibit natural killer cell functions in a transforming growth factor-beta-dependent manner[J].J Exp Med,2005,202(8):1075-1085.DOI:10.1084/jem.20051511.
2017, Vol. 26 
