|Table of Contents|

Analysis of peripheral blood lymphocyte sub-populations variations in patients with esophageal cancer when chemotherapy combined with cellular immunotherapy

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2020 06
Page:
933-938
Research Field:
Publishing date:

Info

Title:
Analysis of peripheral blood lymphocyte sub-populations variations in patients with esophageal cancer when chemotherapy combined with cellular immunotherapy
Author(s):
Jiang Ni; Qiao Guoliang; Wang Xiaoli; Zhou Xinna; Ren Jun
Department of Medical Oncology,Beijing Key Laboratory for Therapeutic Cancer Vaccines,Capital Medical University,Beijing Shijitan Hospital,Beijing 100038,China.
Keywords:
esophageal cancer; cell immune; lymphocyte subsets
PACS:
R735.1
DOI:
10.3969/j.issn.1672-4992.2020.06.014
Abstract:
Objective:To investigate the comparative changes of peripheral blood lymphocyte sub-populations during the entire cycle of chemotherapy combined with autologous adoptive T cell immunotherapy among the esophageal cancers and associated clinical significances.Methods:A total of 113 patients with esophageal cancer who were treated in our hospital were selected.Among them,45 advanced patients received chemotherapy combined with cellular immunotherapy.Peripheral blood lymphocyte subsets were detected in 113 patients before treatment and peripheral blood lymphocyte subsets and tumor biomarkers were detected before and after combined treatment in 45 patients.The correlations were analyzed between cell treatment cycle and peripheral blood lymphocyte subsets,efficacy and peripheral blood lymphocyte subsets,as well as the correlation was analyzed between tumor serological markers and efficacy before treatment.Results:CD8+/CD28+T cell(Tc) was higher in early esophageal cancer patients than in advanced esophageal cancer patients,and CD4+/CD25+T cell（Treg) was lower than in advanced esophageal cancer patients（P values were 0.011 and 0.015,respectively).CD3+T cell(TT),Tc,and myeloid dendritic cells（mDCs) were significantly increased in 45 patients after treatment（P=0.003,P=0.039,P=0.007).Cell immunotherapy was performed in 14 patients with 1 cycle（group A),16 patients with 2 cycles（group B),and 15 patients with 3 cycles or more（group C).TT was significantly increased and Treg was significantly decreased in group A after treatment,TT and Tc were significantly increased in group B after treatment,and changes in three lymphocyte subsets were found in group C,with TT and Treg changes were more significant than those in A,B groups（P=0.003 7,P=0.002).Inthirty patients who achieved objective remission,TT,Tc,natural killer T cell(NKT) and mDCs were significantly increased after treatment while Treg was significantly decreased after treatment.Patients with normal squamous cell carcinoma-associated antigen(SCC) before treatment had better objective response rate than those with increased SCC（P=0.029).Conclusion:The immune unbalance in patients with advanced esophageal cancer is more prevalent than that in patients with early esophageal cancer.Cellular immunotherapy combined with chemotherapy can improve the immune status of patients with esophageal cancer,and the therapeutic effect is related to the improvement of patients' immune function.The increase of SCC may affect the short-term efficacy of patients with esophageal cancer.

References:

[1]Pennathur A,Gibson MK,Jobe BA,et al.Oesophageal carcinoma［J］.Lancet，2013,381(9864):400-412.
[2]Siegel RL,Miller KD,Jemal A.Cancer statistics,2016［J］.CA Cancer J Clin,2016,66(1):7-30.
[3]Chen W,Zheng R,Baade PD,et al.Cancer statisticsin China,2015［J］.CA Cancer J Clin,2016，66(2):115-132.
[4]Topalian SL,Weiner GJ,Pardoll DM.Cancer immunotherapy comes of age［J］.J Clin Oncol,2011,29(36):4828-4836.
[5]Shinto E,Hase K,Hashiguchi Y,et al.CD8+ and FOXP3+ tumor-infiltrating T cells before and after chemoradiotherapy for rectal cancer［J］.Ann Surg Oncol,2014,21(Suppl 3):S414-S421.
[6]Teng F,Meng X,Kong L,et al.Tumor infiltrating lymphocytes,forkhead box P3,programmed death ligand-1,and cytotoxic T lymphocyte-associated antigen-4 expressions before and after neoadjuvant chemoradiation in rectal cancer［J］.Transl Res,2015,166（6):721-732.
[7]Clarke SL,Betts GJ,Plant A,et al.CD4+CD25+FOXP3+ regulatory T cells suppress anti-tumor immune responses in patients with colorectal cancer［J］.PLoS One，2006,27(1):e129.
[8]Tang C,Liao Z,Gomez D,et al.Lymphopenia association with gross tumor volume and lung V5 and its effects on non-small cell lung cancer patient outcomes［J］.Int J Radiat Oncol Biol Phys,2014,89(5):1084-1091.
[9]Jiang N,Qiao G，Wang X,et al.Dendritic cell/cytokine-induced killer cell immunotherapy combined with S-1 in patients with advanced pancreatic cancer:A prospective study［J］.Clin Cancer Res,2017,23(17):5066-5073.
[10]Qiao G,Wang X,Zhou L,et al.Autologous dendritic cell-cytokine induced killer cell immunotherapy combined with S-1 plus cisplatin in patients with advanced gastric cancer:A prospective study［J］.Clin Cancer Res,2019，25(5):1494-1504.
[11]Zhao YJ,Qiao G,Wang X,et al.Combination of DC/CIK adoptive T cell immunotherapy with chemotherapy in advanced non-small-cell lung cancer（NSCLC) patients:A prospective patients' preference-based study（PPPS)［J］.Clin Transl Oncol,2019，21(6):721-728.
[12]Zhao YJ,Jiang N,Song QK,et al.Continuous DC-CIK infusions restore CD8+ cellular immunity,physical activity and improve clinical efficacy in advanced cancer patients unresponsive to conventional treatments［J］.Asian Pac J Cancer Prev,2015,16(6):2419-2423.
[13]Song G,Wang X,Jia J,et al.Elevated level of peripheral CD8(+)CD28(-) T lymphocytes are an independent predictor of progression-free survival in patients with metastatic breast cancer during the course of chemotherapy［J］.Cancer Immunol Immunother,2013,62(6):1123-1130.
[14]Hellstrom I,Raycraft J,Hayden-Ledbetter M,et al．The HE4（WFDC2) protein is a biomarker for ovarian carcinoma［J］.Cancer Res,2003,63(13)：3695-3700．
[15]Wang X,Yu W,Li H,et al.Can the dual-functional capability of CIK cells be used to improve antitumor effects［J］? Cell Immunol,2014,287(1):18-22.
[16]LEI ZY,WANG Y,LUO J,et al.Analysis of T lymphocyte subsets an NK cells in peripheral blood of patients with gastric cancer［J］.J Dig Oncol(Electronic Version),2018,10(4):196-199.［雷子颖,王俞,罗嘉,等.胃癌患者外周血T 淋巴细胞亚群和NK 细胞分析［J］.消化肿瘤杂志(电子版),2018,10(4):196-199.］
[17]WANG CC,LING ZQ,MAO WM,et al.Analysis of peripheral blood lymphocyte subsets in patients with esophageal carcinoma［J］.Chin J Gastroenterol,2011,16(2):103-105．［王长春,凌志强,毛伟敏,等.食管癌患者外周血淋巴细胞亚群分析［J］．胃肠病学,2011,16(2):103-105.］
[18]Motz GT,Coukos G.Deciphering and reversing tumor immune suppression［J］.Immunity,2013,399(1):61-73.
[19]Lindau D,Gielen P,Kroesen M,et al.The immunosuppressive tumour network:Myeloid-derived suppressor cells,regulatory T cells and natural killer T cells［J］.Immunology，2013,138(2):105-115.
[20]Chen B,Liu L,Xu H,et al.Effectiveness of immune therapy combined with chemotherapy on the immune function and recurrence rate of cervical cancer［J］.Exp Ther Med,2015,9(3):1063-1067.
[21]Chu H,Du F,Jiang L,et al.The efficacy of CIK-based immunotherapies for advanced solid tumors［J］.Technol Cancer Res Treat,2017，16(5):577-585.
[22]Zhang L,Mu Y,Zhang A,et al.Cytokine-induced killer cells/dendritic cells-cytokine induced killer cells immunotherapy combined with chemotherapy for treatment of colorectal cancer in China:A Meta-analysis of 29 trials involving 2,610 patients［J］.Oncotarget,2017,8(28):45164-45177.
[23]Mu Y,Wang WH,Xie JP,et al.Efficacy and safety of cord blood-derived dendritic cells plus cytokine-induced killer cells combined with chemotherapy in the treatment of patients with advanced gastric cancer:A randomized phase Ⅱ study［J］.Onco Targets Ther,2016,25(9):4617-4627.
[24]Boeck CL,Amberger DC,Doraneh-Gard F,et al.Significance of frequencies,compositions,and/or antileukemic activity of（DC-stimulated) invariant NKT,NK and CIK cells on the outcome of patients with AML,ALL and CLL［J］.J Immunother,2017，40(6):224-248.
[25]Pan Y,Wu Y,Ji J,et al.Effect of cytokine-induced killer cells on immune function in patients with lung cancer［J］.Oncol Lett,2016，11(4):2827-2834.
[26]Liu Y,Mu Y,Zhang A，et al.Cytokine-induced killer cells/dendritic cells and cytokine-induced killer cells immunotherapy for the treatment of esophageal cancer in China:A Meta-analysis［J］.Onco Targets Ther,2017,29(10):1897-1908.
[27]Shi M,Zhang B,Tang ZR,et al.Autologous cytokine-induced killer cell therapy in clinical trial phase I is safe in patients with primary hepatocellular carcinoma［J］.World J Gastroenterol,2004，10(8):1146-1151.
[28]Schmidt M,Bohm D,von Torne C,et al.The humoral immune system has a key prognostic impact in node-negative breast cancer［J］.Cancer Res,2008,68(13):5405-5413.
[29]Kim R,Emi M,Tanabe K，et al.Tumor-driven evolution of immunosuppressive networks during malignant progression［J］.Cancer Res,2006,66(11):5527-5536.
[30]Ben-Baruch A.Inflammation-associated immune suppression in cancer:The roles played by cytokines,chemokines and additional mediators［J］.Semin Cancer Biol,2006,16(1):38-52.
[31]Chen X,Zhang W,Qian D,et al.Chemoradiotherapy-Induced CD4+ and CD8+ T-cell alterations to predict patient outcomes in esophageal squamous cell carcinoma［J］.Frontier Oncology,2019(9):73.
[32]LI SL,ZHANG B,SONG Y,et al.A study on the changes of T/B/NK lymphocyte subsets in peripheral blood of patients with colorectal cancer before and after chemotherapy［J］.Labeled Immunoassays ＆ Clin Med,2018,25(11):1607-1610.［李世龙,张宝,宋扬,等.结直肠癌患者化疗前后外周血T/B/NK淋巴细胞亚群水平研究［J］.标记免疫分析与临床,2018,25(11):1607-1610.］
[33]SHAN TY,FENG XS,GAO SG,et al.The studies of multi-tumor markers in the detection of aversion and prognosis in esophageal carcinoma［J］.Chin Clin Oncol,2007,12(7):512-516.［单探幽,冯笑山,高社干,等.多种肿瘤标志物对食管癌转移的检测及预后评估［J］.临床肿瘤学杂志,2007,12(7):512-516.］
[34]XIAO Y,SHAO YJ,JIN JH,et al.Prognostic value of SCC-Ag for cervical cancer［J］.Hin J Clin Lab Sci,2017,35(11):808-812.［肖瑶,邵英杰,金建华,等.SCC-Ag在宫颈癌预后中的判断价值［J］.临床检验杂志,2017,35(11):808-812.］

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Last Update: 2020-01-21