山东大学学报 (医学版) ›› 2020, Vol. 1 ›› Issue (8): 67-73.doi: 10.6040/j.issn.1671-7554.0.2020.430
Gang LI*(
),Hao XUE,Wei QIU,Rongrong ZHAO
摘要:
人脑胶质瘤是中枢神经系统最常见的恶性肿瘤,手术切除及放化疗等传统治疗方法效果不理想。近年来,多种免疫治疗策略相继问世,然而由于胶质瘤抑制性免疫微环境的存在,上述疗法仍不尽如人意。探究胶质瘤抑制性免疫微环境的形成机制,是胶质瘤免疫治疗亟需解决的问题。本文结合相关研究领域最新研究进展,对胶质瘤抑制性微环境的研究方向进行总结及展望,为系统全面了解胶质瘤免疫微环境提供重要参考。
中图分类号:
| 1 |
Savage N . Searching for the roots of brain cancer[J]. Nature, 2018, 561 (7724): S50- S51.
doi: 10.1038/d41586-018-06709-2 |
| 2 |
June CH , O'Connor RS , Kawalekar OU , et al. CAR T cell immunotherapy for human cancer[J]. Science, 2018, 359 (6382): 1361- 1365.
doi: 10.1126/science.aar6711 |
| 3 |
Voorwerk L , Slagter M , Horlings HM , et al. Immune induction strategies in metastatic triple-negative breast cancer to enhance the sensitivity to PD-1 blockade: the TONIC trial[J]. Nat Med, 2019, 25 (6): 920- 928.
doi: 10.1038/s41591-019-0432-4 |
| 4 |
Garner H , de Visser KE . Immune crosstalk in cancer progression and metastatic spread: a complex conversation[J]. Nat Rev Immunol, 2020, 20 (8): 483- 497.
doi: 10.1038/s41577-019-0271-z |
| 5 |
Galon J , Bruni D . Tumor immunology and tumor evolution: intertwined histories[J]. Immunity, 2020, 52 (1): 55- 81.
doi: 10.1016/j.immuni.2019.12.018 |
| 6 |
Quail DF , Joyce JA . The microenvironmental landscape of brain tumors[J]. Cancer Cell, 2017, 31 (3): 326- 341.
doi: 10.1016/j.ccell.2017.02.009 |
| 7 |
Xie F , Zhou X , Fang M , et al. Extracellular vesicles in cancer immune microenvironment and cancer immunotherapy[J]. Adv Sci (Weinh), 2019, 6 (24): 1901779.
doi: 10.1002/advs.201901779 |
| 8 |
Cheng J , Meng J , Zhu L , et al. Exosomal noncoding RNAs in Glioma: biological functions and potential clinical applications[J]. Mol Cancer, 2020, 19 (1): 66.
doi: 10.1186/s12943-020-01189-3 |
| 9 |
Qian M , Wang S , Guo X , et al. Hypoxic glioma-derived exosomes deliver microRNA-1246 to induce M2 macrophage polarization by targeting TERF2IP via the STAT3 and NF-kappaB pathways[J]. Oncogene, 2020, 39 (2): 428- 442.
doi: 10.1038/s41388-019-0996-y |
| 10 |
Guo X , Qiu W , Liu Q , et al. Immunosuppressive effects of hypoxia-induced glioma exosomes through myeloid-derived suppressor cells via the miR-10a/Rora and miR-21/Pten Pathways[J]. Oncogene, 2018, 37 (31): 4239- 4259.
doi: 10.1038/s41388-018-0261-9 |
| 11 |
Guo X , Qiu W , Wang J , et al. Glioma exosomes mediate the expansion and function of myeloid-derived suppressor cells through microRNA-29a/Hbp1 and microRNA-92a/Prkar1a pathways[J]. Int J Cancer, 2019, 144 (12): 3111- 3126.
doi: 10.1002/ijc.32052 |
| 12 |
Arvanitis CD , Ferraro GB , Jain RK . The blood-brain barrier and blood-tumour barrier in brain tumours and metastases[J]. Nat Rev Cancer, 2020, 20 (1): 26- 41.
doi: 10.1038/s41568-019-0205-x |
| 13 |
Prinz M , Priller J , Sisodia SS , et al. Heterogeneity of CNS myeloid cells and their roles in neurodegeneration[J]. Nat Neurosci, 2011, 14 (10): 1227- 1235.
doi: 10.1038/nn.2923 |
| 14 | Kettenmann H , Hanisch UK , Noda M , et al. Physiology of microglia[J]. Physiol Rev, 2011, 91 (2): 461- 553. |
| 15 |
Gutmann DH , Kettenmann H . Microglia/brain macrophages as central drivers of brain tumor pathobiology[J]. Neuron, 2019, 104 (3): 442- 449.
doi: 10.1016/j.neuron.2019.08.028 |
| 16 |
Norris GT , Kipnis J . Immune cells and CNS physiology: microglia and beyond[J]. J Exp Med, 2019, 216 (1): 60- 70.
doi: 10.1084/jem.20180199 |
| 17 |
Poon CC , Sarkar S , Yong VW , et al. Glioblastoma-associated microglia and macrophages: targets for therapies to improve prognosis[J]. Brain, 2017, 140 (6): 1548- 1560.
doi: 10.1093/brain/aww355 |
| 18 | Wei J , Chen P , Gupta P , et al. Immune biology of glioma-associated macrophages and microglia: functional and therapeutic implications[J]. Neuro Oncol, 2020, 22 (2): 180- 194. |
| 19 |
Wright-Jin EC , Gutmann DH . Microglia as dynamic cellular mediators of brain function[J]. Trends Mol Med, 2019, 25 (11): 967- 979.
doi: 10.1016/j.molmed.2019.08.013 |
| 20 |
Chen P , Hsu WH , Chang A , et al. Circadian regulator CLOCK recruits immune-suppressive microglia into the GBM tumor microenvironment[J]. Cancer Discov, 2020, 10 (3): 371- 381.
doi: 10.1158/2159-8290.CD-19-0400 |
| 21 |
Abels ER , Maas SLN , Nieland L , et al. Glioblastoma-associated microglia reprogramming is mediated by functional transfer of extracellular miR-21[J]. Cell Rep, 2019, 28 (12): 3105- 3119.
doi: 10.1016/j.celrep.2019.08.036 |
| 22 |
Yu-Ju Wu C , Chen CH , Lin CY , et al. CCL5 of glioma-associated microglia/macrophages regulates glioma migration and invasion via calcium-dependent matrix metalloproteinase 2[J]. Neuro Oncol, 2020, 22 (2): 253- 266.
doi: 10.1093/neuonc/noz189 |
| 23 | Qian J , Luo F , Yang J , et al. TLR2 promotes glioma immune evasion by downregulating MHC class II molecules in microglia[J]. Cancer Immunol Res, 2018, 6 (10): 1220- 1233. |
| 24 |
Guo X , Xue H , Shao Q , et al. Hypoxia promotes glioma-associated macrophage infiltration via periostin and subsequent M2 polarization by upregulating TGF-beta and M-CSFR[J]. Oncotarget, 2016, 7 (49): 80521- 80542.
doi: 10.18632/oncotarget.11825 |
| 25 |
Zong CC . Single-cell RNA-seq study determines the ontogeny of macrophages in glioblastomas[J]. Genome Biol, 2017, 18 (1): 235.
doi: 10.1186/s13059-017-1375-z |
| 26 |
Yan D , Kowal J , Akkari L , et al. Inhibition of colony stimulating factor-1 receptor abrogates microenvironment-mediated therapeutic resistance in gliomas[J]. Oncogene, 2017, 36 (43): 6049- 6058.
doi: 10.1038/onc.2017.261 |
| 27 |
Sylvestre M , Crane CA , Pun SH . Progress on modulating tumor-associated macrophages with biomaterials[J]. Adv Mater, 2020, 32 (13): e1902007.
doi: 10.1002/adma.201902007 |
| 28 |
Vetsika EK , Koukos A , Kotsakis A . Myeloid-derived suppressor cells: major figures that shape the immunosuppressive and angiogenic network in cancer[J]. Cells, 2019, 8 (12): 1647.
doi: 10.3390/cells8121647 |
| 29 |
Kumar V , Patel S , Tcyganov E , et al. The nature of myeloid-derived suppressor cells in the tumor microenvironment[J]. Trends Immunol, 2016, 37 (3): 208- 220.
doi: 10.1016/j.it.2016.01.004 |
| 30 |
Waziri A . Glioblastoma-derived mechanisms of systemic immunosuppression[J]. Neurosurg Clin N Am, 2010, 21 (1): 31- 42.
doi: 10.1016/j.nec.2009.08.005 |
| 31 |
Chae M , Peterson TE , Balgeman A , et al. Increasing glioma-associated monocytes leads to increased intratumoral and systemic myeloid-derived suppressor cells in a murine model[J]. Neuro Oncol, 2015, 17 (7): 978- 991.
doi: 10.1093/neuonc/nou343 |
| 32 |
Chang AL , Miska J , Wainwright DA , et al. CCL2 Produced by the glioma microenvironment is essential for the recruitment of regulatory T cells and myeloid-derived suppressor cells[J]. Cancer Res, 2016, 76 (19): 5671- 5682.
doi: 10.1158/0008-5472.CAN-16-0144 |
| 33 |
Flores-Toro JA , Luo D , Gopinath A , et al. CCR2 inhibition reduces tumor myeloid cells and unmasks a checkpoint inhibitor effect to slow progression of resistant murine gliomas[J]. Proc Natl Acad Sci U S A, 2020, 117 (2): 1129- 1138.
doi: 10.1073/pnas.1910856117 |
| 34 |
Le Gall CM , Weiden J , Eggermont LJ , et al. Dendritic cells in cancer immunotherapy[J]. Nat Mater, 2018, 17 (6): 474- 475.
doi: 10.1038/s41563-018-0093-6 |
| 35 |
Yan J , Zhao Q , Gabrusiewicz K , et al. FGL2 promotes tumor progression in the CNS by suppressing CD103(+) dendritic cell differentiation[J]. Nat Commun, 2019, 10 (1): 448.
doi: 10.1038/s41467-018-08271-x |
| 36 | 刘鸿宇, 沈少平, 杨霖, 等. 树突状细胞疫苗在恶性胶质瘤免疫治疗中的应用[J]. 中国现代神经疾病杂志, 2020, 20 (2): 119- 126. |
| LIU Hongyu , SHEN Shaoping , YANG Lin , et al. The application of dendritic cells vaccination in malignant glioma[J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2020, 20 (2): 119- 126. | |
| 37 |
Nicolas-Avila JA , Adrover JM , Hidalgo A . Neutrophils in homeostasis, immunity, and cancer[J]. Immunity, 2017, 46 (1): 15- 28.
doi: 10.1016/j.immuni.2016.12.012 |
| 38 |
Bertaut A , Truntzer C , Madkouri R , et al. Blood baseline neutrophil count predicts bevacizumab efficacy in glioblastoma[J]. Oncotarget, 2016, 7 (43): 70948- 70958.
doi: 10.18632/oncotarget.10898 |
| 39 |
Liang J , Piao Y , Holmes L , et al. Neutrophils promote the malignant glioma phenotype through S100A4[J]. Clin Cancer Res, 2014, 20 (1): 187- 198.
doi: 10.1158/1078-0432.CCR-13-1279 |
| 40 |
Khan S , Mittal S , McGee K , et al. Role of neutrophils and myeloid-derived suppressor cells in glioma progression and treatment resistance[J]. Int J Mol Sci, 2020, 21 (6): 1954.
doi: 10.3390/ijms21061954 |
| 41 |
Shaul ME , Fridlender ZG . Cancer-related circulating and tumor-associated neutrophils-subtypes, sources and function[J]. FEBS J, 2018, 285 (23): 4316- 4342.
doi: 10.1111/febs.14524 |
| 42 |
van der Leun AM , Thommen DS , Schumacher TN . CD8(+) T cell states in human cancer: insights from single-cell analysis[J]. Nat Rev Cancer, 2020, 20 (4): 218- 232.
doi: 10.1038/s41568-019-0235-4 |
| 43 |
Sharonov GV , Serebrovskaya EO , Yuzhakova DV , et al. B cells, plasma cells and antibody repertoires in the tumour microenvironment[J]. Nat Rev Immunol, 2020, 20 (5): 294- 307.
doi: 10.1038/s41577-019-0257-x |
| 44 | Miska J , Lee-Chang C , Rashidi A , et al. HIF-1alpha is ametabolic switch between glycolytic-driven migration and oxidative phosphorylation-driven immunosuppression of tregs in glioblastoma[J]. Cell Rep, 2019, 27 (1): 226- 237. |
| 45 |
Togashi Y , Shitara K , Nishikawa H . Regulatory T cells in cancer immunosuppression-implications for anticancer therapy[J]. Nat Rev Clin Oncol, 2019, 16 (6): 356- 371.
doi: 10.1038/s41571-019-0175-7 |
| 46 |
Nehama D , Di Ianni N , Musio S , et al. B7-H3-redirected chimeric antigen receptor T cells target glioblastoma and neurospheres[J]. EBioMedicine, 2019, 47: 33- 43.
doi: 10.1016/j.ebiom.2019.08.030 |
| 47 | Choi BD , Yu X , Castano AP , et al. CRISPR-Cas9 disruption of PD-1 enhances activity of universal EGFRvIII CAR T cells in a preclinical model of human glioblastoma[J]. J Immunother Cancer, 2019, 7 (1): 304. |
| 48 |
Figueroa J , Phillips LM , Shahar T , et al. Exosomes from glioma-associated mesenchymal stem cells increase the tumorigenicity of glioma stem-like cells via transfer of miR-1587[J]. Cancer Res, 2017, 77 (21): 5808- 5819.
doi: 10.1158/0008-5472.CAN-16-2524 |
| 49 | Shahar T , Rozovski U , Hess KR , et al. Percentage of mesenchymal stem cells in high-grade glioma tumor samples correlates with patient survival[J]. Neuro Oncol, 2017, 19 (5): 660- 668. |
| 50 |
Tumangelova-Yuzeir K , Naydenov E , Ivanova-Todorova E , et al. Mesenchymal stem cells derived and cultured from glioblastoma multiforme increase tregs, downregulate Th17, and induce the tolerogenic phenotype of monocyte-derived cells[J]. Stem Cells Int, 2019, 2019: 6904638.
doi: 10.1155/2019/6904638.eCollection2019 |
| 51 |
Cloughesy TF , Mochizuki AY , Orpilla JR , et al. Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma[J]. Nat Med, 2019, 25 (3): 477- 486.
doi: 10.1038/s41591-018-0337-7 |
| 52 |
Schalper KA , Rodriguez-Ruiz ME , Diez-Valle R , et al. Neoadjuvant nivolumab modifies the tumor immune microenvironment in resectable glioblastoma[J]. Nat Med, 2019, 25 (3): 470- 476.
doi: 10.1038/s41591-018-0339-5 |
| 53 |
Zhao J , Chen AX , Gartrell RD , et al. Immune and genomic correlates of response to anti-PD-1 immunotherapy in glioblastoma[J]. Nat Med, 2019, 25 (3): 462- 469.
doi: 10.1038/s41591-019-0349-y |
| [1] | 王琳琳 孙美丽 孙玉萍 张楠 刘传勇. 中心体α-微管蛋白、γ-微管蛋白在脑胶质瘤中的表达及其与Survivin表达的相关性研究[J]. 山东大学学报(医学版), 2209, 47(6): 103-. |
| [2] | 郭姝画,樊扬,田风,王传新,杜鲁涛,李培龙,郭兴,徐硕. 微原纤维相关蛋白3在调控胶质瘤干细胞间充质表型转化中的作用[J]. 山东大学学报 (医学版), 2024, 62(6): 9-16. |
| [3] | 宋兆录,董正璇,彭传真,黄彩娜,胡克清,黄永胜,阎磊. 肾透明细胞癌中预后相关RNA编辑位点的筛选[J]. 山东大学学报 (医学版), 2023, 61(9): 69-78. |
| [4] | 李夕凤,李红梅. 脑脊液CXCL10:抗NMDAR脑炎潜在的生物学标志物[J]. 山东大学学报 (医学版), 2023, 61(6): 47-52. |
| [5] | 胡立勇,钟浩,房娟娟,国巍,张雨露,范医东. 基于数据库分析CCR基因对肾透明细胞癌预后的预测价值[J]. 山东大学学报 (医学版), 2023, 61(4): 49-55. |
| [6] | 朱正阳,沈靖菲,陈思璇,叶梅萍,杨惠泉,周佳南,梁雪,张鑫,张冰. 磁敏感加权成像不同影像组学模型预测胶质瘤IDH基因突变[J]. 山东大学学报 (医学版), 2023, 61(12): 44-50. |
| [7] | 秦静,杨飞,陈谦,夏涵岱,刘延国,王秀问. 晚期驱动基因阴性、PD-L1表达阴性非鳞非小细胞肺癌一线治疗方案的网状Meta分析[J]. 山东大学学报 (医学版), 2022, 60(7): 74-82. |
| [8] | 李华玉,时萧寒,张新蕊,李峰. 203例胶质瘤患者睡眠障碍与炎症细胞因子的关联分析[J]. 山东大学学报 (医学版), 2022, 60(12): 26-30. |
| [9] | 高会江,魏煜程. 微创袖式肺叶切除手术:免疫治疗时代的机遇和挑战[J]. 山东大学学报 (医学版), 2022, 60(11): 23-27. |
| [10] | 于金明,颜薇薇,陈大卫. 肺癌放射免疫新实践[J]. 山东大学学报 (医学版), 2021, 59(9): 1-8. |
| [11] | 邓晓惠,郭玲. 免疫治疗在胚胎反复种植失败中的应用进展[J]. 山东大学学报 (医学版), 2021, 59(8): 32-37. |
| [12] | 孙庆杰,张怡莎,管尚慧,凤志慧. 丙戊酸对134例放疗神经胶质瘤患者预后生存和肿瘤复发的影响[J]. 山东大学学报 (医学版), 2021, 59(8): 80-85. |
| [13] | 顾金海,路宁,顾珈榕,文玉军,强媛媛,和祯泉,杨勇,王峰,孙涛,牛建国. 胶质瘤细胞与血管内皮细胞的信号Crosstalk对肿瘤细胞增殖和侵袭的影响[J]. 山东大学学报 (医学版), 2021, 59(2): 1-6. |
| [14] | 庞兆飞,柳勇,赵小刚,闫涛,陈效伟,杜贾军. 基于公共数据库构建肺腺癌肿瘤干性评分模型预测免疫治疗疗效[J]. 山东大学学报 (医学版), 2021, 59(11): 19-28. |
| [15] | 宋珍珍,孙小玲,李海鸥,王芳,张冉,于德新. 120例胶质瘤及瘤周水肿MRI影像组学在评估肿瘤复发中的价值[J]. 山东大学学报 (医学版), 2021, 59(11): 53-60. |
|
||