骨肉瘤免疫靶向治疗相关机制的研究进展
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摘要
骨肉瘤(OS)起源于间叶组织,在青少年及老年人群中呈特征性双高峰分布,是发病率最高的原发性恶性骨肿瘤之一。免疫靶向治疗能阻断肿瘤细胞信号传递通路,促进癌细胞凋亡,是近年来继手术、化疗后抗OS治疗有效手段之一。本文对OS免疫靶向治疗相关机制最新研究进展作一综述,为临床治疗提供理论依据。
Osteosarcoma,originated from mesenchymal tissue,is one of the highest incidence of primary malignant bone tumors which were characteristic double peak distribution both in adolescents and elderly. Immune-targeted therapy could block the tumor cell signaling pathway and promote cancer cell death by apoptosis. Immune-targeted therapy is an effective treatment of anti-osteosarcoma after surgery and chemotherapy in recent years. The paper reviews the advances in latest research on the related mechanisms of the immune-targeted therapy on osteosarcoma,and hope to provide a theoretical basis for clinical treatment.
Osteosarcoma,originated from mesenchymal tissue,is one of the highest incidence of primary malignant bone tumors which were characteristic double peak distribution both in adolescents and elderly. Immune-targeted therapy could block the tumor cell signaling pathway and promote cancer cell death by apoptosis. Immune-targeted therapy is an effective treatment of anti-osteosarcoma after surgery and chemotherapy in recent years. The paper reviews the advances in latest research on the related mechanisms of the immune-targeted therapy on osteosarcoma,and hope to provide a theoretical basis for clinical treatment.
引文
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[25]Huang JC,Cui ZF,Chen SM,et al.NVP-BEZ235 synergizes cisplatin sensitivity in osteosarcoma[J].Oncotarget,2017,9(12):10483-10496.
[26]Navid F,Santana VM,Neel M,et al.A phase II trial evaluating the feasibility of bevacizumab to standard osteosarcoma therapy[J].Int J Cancer,2017,141(7):1469-1477.
[27]Yang M,Liu B,Jin L,et al.Estrogen receptorβexhibited antitumor effects on osteosarcoma cells by regulating integrin,IAP,NF-kB/BCL-2 and PI3K/Akt signal pathway[J].J Bone Oncol,2017,9:15-20.
[2]Mori K,Rédini F,Gouin F,et al.Osteosarcoma:current status of immunotherapy and future trends(Review)[J].Oncol Rep,2006,15(3):693-700.
[3]Dobbelstein M,Moll U.Targeting tumour-supportive cellular machineries in anticancer drug development[J].Nat Rev Drug Discov,2014,13(3):179-196.
[4]Nefedova Y,Nagaraj S,Rosenbauer A,et al.Regulation of dendritic cell differentiation and antitumor immune response in cancer by pharmacologic-selective inhibition of the janus-activated kinase 2/signal transducers and activators of transcription 3 pathway[J].Cancer Res,2005,65(20):9525-9535.
[5]Seeger JM,Schmidt P,Brinkmann K,et al.The proteasome inhibitor bortezomib sensitizes melanoma cells toward adoptive CTLattack[J].Cancer Res,2010,70(5):1825-1834.
[6]Roberts SS,Chou AJ,Cheung NK.Immunotherapy of Childhood Sarcomas[J].Front Oncol,2015,5:181.
[7]Mackall CL,Merchant MS,Fry TJ.Immune-based therapies for childhood cancer[J].Nat Rev Clin Oncol,2014,11(12):693-703.
[8]Steinman RM,Mellman I.Immunotheraphy:bewitched,bothered,and bewildered no more[J].Science,2004,305(5681):197-200.
[9]Guma SR,Lee DA,Ling Y,et al.Aerosol interleukin-2 induces natural killer cell proliferation in the lung and combination therapy improves the survival of mice with osteosarcoma lung metastasis[J].Pediatr Blood Cancer,2014,61(8):1362-1368.
[10]Meyers PA,Schwartz CL,Krailo MD,et al.Osteosarcoma:the addition of muramyl tripeptide to chemotherapy improves overall survival-a report from the Children's Oncology Group[J].J Clin Oncol,2008,26(4):633-638.
[11]Hou TZ,Olbrich P,Soto JML,et al.Study of an extended family with CTLA-4 deficiency suggests a CD28/CTLA-4 independent mechanism responsible for differences in disease manifestations and severity[J].Clin Immunol,2018,188:94-102.
[12]Snyder A,Makarov V,Merghoub T,et al.Genetic basis for clinical response to CTLA-4 blockade in melanoma[J].N Engl J Med,2014,371(23):2189-2199.
[13]Rizvi NA,Hellmann MD,Snyder A,et al.Cancer immunology.Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer[J].Science,2015,348(6230):124-128.
[14]Lussier DM,O'Neill L,Nieves LM,et al.Enhanced T-cell immunity to osteosarcoma through antibody blockade of PD-1/PD-L1 interactions[J].J Immunother,2015,38(3):96-106.
[15]Lussier DM,Johnson JL,Hingorani P,et al.Combination immunotherapy withα-CTLA-4 andα-PD-L1 antibody blockade prevents immune escape and leads to complete control of metastatic osteosarcoma[J].J Immunother Cancer,2015,3:21.
[16]Guan Y,Zhang R,Peng Z,et al.Inhibition of IL-18-mediated myeloid derived suppressor cell accumulation enhances anti-PD1 efficacy against osteosarcoma cancer[J].J Bone Oncol,2017,9:59-64.
[17]Beristain AG,Narala SR,Di Grappa MA,et al.Homotypic RANKsignaling differentially regulates proliferation,motility and cell survival in osteosarcoma and mammary epithelial cells[J].J Cell Sci,2012,125:943-955.
[18]Roth M,Barris DM,Piperdi S,et al.Targeting glycoprotein NMBwith antibody-drug conjugate,glembatumumab vedotin,for the treatment of osteosarcoma[J].Pediatr Blood Cancer,2016,63(1):32-38.
[19]Poon VI,Roth M,Piperdi S,et al.Ganglioside GD2 expression is maintained upon recurrence in patients with osteosarcoma[J].Clin Sarcoma Res,2015,5(1):4.
[20]Kiyuna T,Tome Y,Uehara F,et al.Tumor-targeting salmonella typhimurium A1-R inhibits osteosarcoma angiogenesis in the in vivo gelfoamassay visualized by color-coded imaging[J].Anticancer Res,2018,38(1):159-164.
[21]李朝旭,张浚哲,王胜涛,等.雷公藤红素经过TRAIL途径增强γδT细胞对骨肉瘤细胞株HOS的杀伤作用[J].中国免疫学杂志,2016,32(12):1777-1780.Li ZX,Zhang JZ,Wang ST,et al.Celastrol increases osteosarcoma cells line HOS lysis byγδT cells through TRAIL way[J].Chin JImmunol,2016,32(12):1777-1780.
[22]Mason NJ,Gnanandarajah JS,Engiles JB,et al.Immunotherapy with a HER2-Targeting listeria induces HER2-Specific immunity and demonstrates potential therapeutic effects in a phase I trial in canine osteosarcoma[J].Clin Cancer Res,2016,22(17):4380-4390.
[23]Araki K,Youngblood B,Ahmed R,et al.The role of m TOR in memory CD8 T-cell differentiation[J].Immunol Rev,2010,235(1):234-243.
[24]Anderson JL,Park A,Akiyama R,et al.Evaluation of in vitro activity of the class I PI3K inhibitor buparlisib(BKM120)in pediatric bone and soft tissue sarcomas[J].PLoS One,2015,10(9):e0133610.
[25]Huang JC,Cui ZF,Chen SM,et al.NVP-BEZ235 synergizes cisplatin sensitivity in osteosarcoma[J].Oncotarget,2017,9(12):10483-10496.
[26]Navid F,Santana VM,Neel M,et al.A phase II trial evaluating the feasibility of bevacizumab to standard osteosarcoma therapy[J].Int J Cancer,2017,141(7):1469-1477.
[27]Yang M,Liu B,Jin L,et al.Estrogen receptorβexhibited antitumor effects on osteosarcoma cells by regulating integrin,IAP,NF-kB/BCL-2 and PI3K/Akt signal pathway[J].J Bone Oncol,2017,9:15-20.