CD_(47)在胃癌免疫治疗中的研究进展
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摘要
免疫系统对抑制肿瘤的发生、发展具有重要作用,肿瘤细胞能被免疫细胞清除,故通过免疫系统消灭肿瘤细胞在治疗各种恶性肿瘤中显示出显著疗效。肿瘤细胞通过高表达CD_(47)与巨噬细胞表面的信号调节蛋白α相结合逃避机体的免疫监视,从而促进肿瘤的发展。因此,CD_(47)在肿瘤组织中的表达及抗CD_(47)抗体靶向免疫治疗成为研究热点。随着检测胃癌组织中CD_(47)的表达情况、开展体外胃癌细胞实验及动物模型实验、抗CD_(47)抗体等研究的深入,未来抗CD_(47)抗体用于胃癌免疫治疗将成为新途径。
The immune system plays an important role in inhibiting the occurrence and development of tumors,and tumor cells can be cleared by immune cells. Therefore,the elimination of tumor cells by the immune system shows a significant effect in the treatment of various malignant tumors. By highly expressing CD_(47),tumor cells combine with the signal regulatory protein α on the surface of macrophages to evade the immune surveillance of the body,thus promoting the development of tumors. Therefore,the expression of CD_(47) in tumor tissues and the targeted immunotherapy of anti-CD_(47) antibodies have become a research hotspot. With the deepening research on detecting the expression of CD_(47) in gastric cancer tissues,carrying out in vitro gastric cancer cell experiment,animal model experiment and anti-CD_(47) antibody,the application of antiCD_(47) antibody to immunotherapy for gastric cancer will become a new approach in the future.
The immune system plays an important role in inhibiting the occurrence and development of tumors,and tumor cells can be cleared by immune cells. Therefore,the elimination of tumor cells by the immune system shows a significant effect in the treatment of various malignant tumors. By highly expressing CD_(47),tumor cells combine with the signal regulatory protein α on the surface of macrophages to evade the immune surveillance of the body,thus promoting the development of tumors. Therefore,the expression of CD_(47) in tumor tissues and the targeted immunotherapy of anti-CD_(47) antibodies have become a research hotspot. With the deepening research on detecting the expression of CD_(47) in gastric cancer tissues,carrying out in vitro gastric cancer cell experiment,animal model experiment and anti-CD_(47) antibody,the application of antiCD_(47) antibody to immunotherapy for gastric cancer will become a new approach in the future.
引文
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[4]张敏,李佳,俞德超.靶向抗肿瘤单克隆抗体药物应用的现状和展望[J].中国肿瘤生物治疗杂志,2017,24(9):929-937.
[5]支馨仪,刘岩厚,高晶,等.巨噬细胞在肿瘤免疫治疗中的研究进展[J].中国免疫学杂志,2018,34(2):277-281,286.
[6]甘波,杨乐莹,李媛媛,等.CD47和SIRPα1在胃癌组织中的表达和意义[A].首届浙赣两省肿瘤研究交流会论文汇编,衢州,2012[C].杭州:浙江省科学技术协会,2012:361-362.
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[8]Yoshida K,Tsujimoto H,Matsumura K,et al.CD47is an adverse prognostic factor and a therapeutic target in gastric cancer[J].Cancer Med,2015,4(9):1322-1333.
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[11]Tong B,Wang M.CD47is a novel potent immunotherapy target in human malignancies:Current studies and future promises[J].Future Oncol,2018,14(21):2179-2188.
[12]Kershaw MH,Smyth MJ.Immunology.Making macrophages eat cancer[J].Science,2013,341(6141):41-42.
[13]Vonderheide RH.CD47blockade as another immune checkpoint therapy for cancer[J].Nat Med,2015,21(10):1122-1123.
[14]徐莲,高树峰,张少容.CD47在肿瘤防治中的作用[J].广东医学,2014,35(18):2945-2947.
[15]Liu X,Kwon H,Li Z,et al.Is CD47an innate immune checkpoint for tumor evasion?[J].J Hematol oncol,2017,10(1):12.
[16]Huang Y,Ma Y,Gao P,et al.Targeting CD47:The achievements and concerns of current studies on caner immunotherapy[J].J Thorac Dis,2017,9(2):E168-174.
[17]Huang H,Chen A,Wang T,et al.Detecting cell-in-cell structures in human tumor samples by E-cadherin/CD68/CD45triple staining[J].Oncotarget,2015,6(24):20278-20287.
[18]Wang M,Zhou C,Chen A,et al.Macrophages are involved in cell-in-cell structures in human tumors[J].Macrophage,2016,3:e1101.
[19]Ostuni R,Kratochvill F,Murray PJ,et al.Macrophages and caner:From mechanisms to therapeutic implications[J].Trends immunol,2015,36(4):229-239.
[20]Weiskopf K,Ring AM,Ho CC,et al.Engineered SIRPαvariants as immunotherapeutic adjuvants to anticancer antibodies[J].Science,2013,341(6141):88-91.
[21]Liu X,Pu Y,Cron K,et al.CD47 blockade triggers T cell-mediated destruction of immunogenic tumors[J].Nat Med,2015,21(10):1209-1215.
[22]Wang HS,Pei F,Chen Z,et al.Increased apoptosis of inflamed odontoblasts is associated with CD47loss[J].J Dent Res,2016,95(6):697-703.
[23]Chao MP,Alizadeh AA,Tang C,et al.Therapeutic antibody targeting of CD47eliminates human acute lymphoblastic leukemia[J].Cancer Res,2011,71(4):1374-1384.
[24]Rauh MJ,Ho V,Pereira C,et al.SHIP represses the generation of alternatively activated macrophage[J].Immunity,2005,23(4):361-374.
[25]赵立坤,韩思奇.表阿霉素和抗CD47抗体联合治疗乳腺癌的体外实验研究[J].中国免疫学杂志,2014,30(10):1360-1363.
[26]Weiskopf K,Jahchan NS,Schnorr PJ,et al.CD47-blocking immunotherapies stimulate macrophage-mediated destruction of small-cell lung cancer[J].J Clin Invest,2016,126(7):2610-2620.
[27]Abe H,Saito R,Ichimura T,et al.CD47expression in EpsteinBarr virus-associated gastric carcinoma:Coexistence with tumor immunity lowering the ratio of CD+8/Foxp+3T cells[J].Virchows Arch,2018,472(4):643-651.
[28]Majeti R,Chao MP,Alizadeh AA,et al.CD47is an adverse prognostic factor and therapeutic antibody target on human acute myeloid leukemia stem cells[J].Cell,2009,138(2):286-299.
[29]黄丽芳,李国华.SIRPα及其配体CD47在巨噬细胞吞噬过程中的作用[J].南昌大学学报(医学版),2016,56(5):85-88.
[30]Ansell S,Chen RW,Flinn IW,et al.A phase 1 study of TTI-621,a novel immune checkpoint inhibitor targeting CD47,in patients with relapsed or refractory hematologic malignancies[J].Blood,2016,128(22):1812.
[31]Chao MP,Mc Kenna KM,Cha A,et al.Abxtract PR13:The antiCD47antibody Hu5F9-G4 is a novel immune checkpoint inhibitor with Synergistic efficacy in combination with clinically active cancer targeting antibodies[J].Cancer Immunol Res,2016,4:1023-1028.
[32]Sikic BI,Narayanan S,Colevas AD,et al.A first-in-human,first-inclass phaseⅠtrial of the anti-CD47antibody Hu5F9-G4 in patients with advanced cancers[J].J Clin Oncol,2016,34:3019.
[33]Petrova PS,Viller NN,Wong M,et al.TT-621(SIRPαFc):ACD47-blocking innate immune checkpoint inhibitor with broad antitumor activity and minimal erythrocyte binding[J].Clin Cancer Res,2017,23(4):1068-1069.
[34]Liu J,Wang L,Zhao F,et al.Pre-clinical development of a humanized anti-CD47antibody with anti-cancer therapeutic potential[J].PLo S One,2015,10(9):e0137345.
[35]牛海涛,袁芄.晚期胃癌的靶向及免疫治疗进展[J].中国临床医生杂志,2018,46(4):384-387.
[36]王颖超,冯磊,殷楚云,等.抗CD47抗体联合阿糖胞苷靶向治疗NOD/SCID小鼠单核细胞白血病的研究[J].中国当代儿科杂志,2013,15(7):577-582.
[37]Yang Y,Guo R,Chen Q,et al.A novel bispecific antibody fusion protein co-targeting EGFR and CD47with enhanced therapeutic index[J].Biotechnol Lett,2018,40(5):789-795.
[38]Zeng D,Sun Q,Chen A,et al.A fully human anti-CD47blocking antibody with therapeutic potential for cancer[J].Oncotarget,2016,7(50):83040-83050.
[2]Chang YR,Han DS,Kong SH,et al.The value of palliative gastrectomy in gastric cancer with distant metastasis[J].Ann Surg Oncol,2012,19(4):1231-1239.
[3]高秀娟,巴一.胃癌的免疫治疗研究进展[J].中国肿瘤临床,2018,45(3):152-156.
[4]张敏,李佳,俞德超.靶向抗肿瘤单克隆抗体药物应用的现状和展望[J].中国肿瘤生物治疗杂志,2017,24(9):929-937.
[5]支馨仪,刘岩厚,高晶,等.巨噬细胞在肿瘤免疫治疗中的研究进展[J].中国免疫学杂志,2018,34(2):277-281,286.
[6]甘波,杨乐莹,李媛媛,等.CD47和SIRPα1在胃癌组织中的表达和意义[A].首届浙赣两省肿瘤研究交流会论文汇编,衢州,2012[C].杭州:浙江省科学技术协会,2012:361-362.
[7]Sudo T,Takahashi Y,Sawada G,et al.Significance of CD47expression in gastric cancer[J].Oncol Lett,2017,14(1):801-809.
[8]Yoshida K,Tsujimoto H,Matsumura K,et al.CD47is an adverse prognostic factor and a therapeutic target in gastric cancer[J].Cancer Med,2015,4(9):1322-1333.
[9]Lindberg FP,Lublin DM,Telen MJ,et al.Rh-related antigen CD47is the signal-transducer integrin-associated protein[J].J Biol Chem,1994,269(3):1567-1570.
[10]杨赟,张子恒,张朋飞.CD47分子与抗肿瘤免疫[J].中国生物化学与分子生物学报,2018,34(3):262-266.
[11]Tong B,Wang M.CD47is a novel potent immunotherapy target in human malignancies:Current studies and future promises[J].Future Oncol,2018,14(21):2179-2188.
[12]Kershaw MH,Smyth MJ.Immunology.Making macrophages eat cancer[J].Science,2013,341(6141):41-42.
[13]Vonderheide RH.CD47blockade as another immune checkpoint therapy for cancer[J].Nat Med,2015,21(10):1122-1123.
[14]徐莲,高树峰,张少容.CD47在肿瘤防治中的作用[J].广东医学,2014,35(18):2945-2947.
[15]Liu X,Kwon H,Li Z,et al.Is CD47an innate immune checkpoint for tumor evasion?[J].J Hematol oncol,2017,10(1):12.
[16]Huang Y,Ma Y,Gao P,et al.Targeting CD47:The achievements and concerns of current studies on caner immunotherapy[J].J Thorac Dis,2017,9(2):E168-174.
[17]Huang H,Chen A,Wang T,et al.Detecting cell-in-cell structures in human tumor samples by E-cadherin/CD68/CD45triple staining[J].Oncotarget,2015,6(24):20278-20287.
[18]Wang M,Zhou C,Chen A,et al.Macrophages are involved in cell-in-cell structures in human tumors[J].Macrophage,2016,3:e1101.
[19]Ostuni R,Kratochvill F,Murray PJ,et al.Macrophages and caner:From mechanisms to therapeutic implications[J].Trends immunol,2015,36(4):229-239.
[20]Weiskopf K,Ring AM,Ho CC,et al.Engineered SIRPαvariants as immunotherapeutic adjuvants to anticancer antibodies[J].Science,2013,341(6141):88-91.
[21]Liu X,Pu Y,Cron K,et al.CD47 blockade triggers T cell-mediated destruction of immunogenic tumors[J].Nat Med,2015,21(10):1209-1215.
[22]Wang HS,Pei F,Chen Z,et al.Increased apoptosis of inflamed odontoblasts is associated with CD47loss[J].J Dent Res,2016,95(6):697-703.
[23]Chao MP,Alizadeh AA,Tang C,et al.Therapeutic antibody targeting of CD47eliminates human acute lymphoblastic leukemia[J].Cancer Res,2011,71(4):1374-1384.
[24]Rauh MJ,Ho V,Pereira C,et al.SHIP represses the generation of alternatively activated macrophage[J].Immunity,2005,23(4):361-374.
[25]赵立坤,韩思奇.表阿霉素和抗CD47抗体联合治疗乳腺癌的体外实验研究[J].中国免疫学杂志,2014,30(10):1360-1363.
[26]Weiskopf K,Jahchan NS,Schnorr PJ,et al.CD47-blocking immunotherapies stimulate macrophage-mediated destruction of small-cell lung cancer[J].J Clin Invest,2016,126(7):2610-2620.
[27]Abe H,Saito R,Ichimura T,et al.CD47expression in EpsteinBarr virus-associated gastric carcinoma:Coexistence with tumor immunity lowering the ratio of CD+8/Foxp+3T cells[J].Virchows Arch,2018,472(4):643-651.
[28]Majeti R,Chao MP,Alizadeh AA,et al.CD47is an adverse prognostic factor and therapeutic antibody target on human acute myeloid leukemia stem cells[J].Cell,2009,138(2):286-299.
[29]黄丽芳,李国华.SIRPα及其配体CD47在巨噬细胞吞噬过程中的作用[J].南昌大学学报(医学版),2016,56(5):85-88.
[30]Ansell S,Chen RW,Flinn IW,et al.A phase 1 study of TTI-621,a novel immune checkpoint inhibitor targeting CD47,in patients with relapsed or refractory hematologic malignancies[J].Blood,2016,128(22):1812.
[31]Chao MP,Mc Kenna KM,Cha A,et al.Abxtract PR13:The antiCD47antibody Hu5F9-G4 is a novel immune checkpoint inhibitor with Synergistic efficacy in combination with clinically active cancer targeting antibodies[J].Cancer Immunol Res,2016,4:1023-1028.
[32]Sikic BI,Narayanan S,Colevas AD,et al.A first-in-human,first-inclass phaseⅠtrial of the anti-CD47antibody Hu5F9-G4 in patients with advanced cancers[J].J Clin Oncol,2016,34:3019.
[33]Petrova PS,Viller NN,Wong M,et al.TT-621(SIRPαFc):ACD47-blocking innate immune checkpoint inhibitor with broad antitumor activity and minimal erythrocyte binding[J].Clin Cancer Res,2017,23(4):1068-1069.
[34]Liu J,Wang L,Zhao F,et al.Pre-clinical development of a humanized anti-CD47antibody with anti-cancer therapeutic potential[J].PLo S One,2015,10(9):e0137345.
[35]牛海涛,袁芄.晚期胃癌的靶向及免疫治疗进展[J].中国临床医生杂志,2018,46(4):384-387.
[36]王颖超,冯磊,殷楚云,等.抗CD47抗体联合阿糖胞苷靶向治疗NOD/SCID小鼠单核细胞白血病的研究[J].中国当代儿科杂志,2013,15(7):577-582.
[37]Yang Y,Guo R,Chen Q,et al.A novel bispecific antibody fusion protein co-targeting EGFR and CD47with enhanced therapeutic index[J].Biotechnol Lett,2018,40(5):789-795.
[38]Zeng D,Sun Q,Chen A,et al.A fully human anti-CD47blocking antibody with therapeutic potential for cancer[J].Oncotarget,2016,7(50):83040-83050.