
浏览全部资源
扫码关注微信
1.重庆大学附属肿瘤医院肿瘤学实验室、肿瘤转移与个体化诊治转化研究重庆市重点实验室,重庆 400030
2.重庆大学医学院、重庆大学附属肿瘤医院,重庆 400030
黄一薇,Email:huangyw05@126.com ,研究方向:质谱检测及组学研究。
赵 毅,Email:yizhao@cqu.edu.cn。
收稿:2024-01-15,
修回:2024-03-11,
录用:2024-04-24,
纸质出版:2025-01-28
移动端阅览
黄一薇,向廷秀,刘星河,等.质谱流式成像技术及其在肿瘤研究中的应用进展[J].重庆医科大学学报,2025,50(1):6-13.
Huang Yiwei,Xiang Tingxiu,Liu Xinghe,et al.Imaging mass cytometry technology and its application in tumor research[J].Journal of Chongqing Medical University,2025,50(1):6-13.
黄一薇,向廷秀,刘星河,等.质谱流式成像技术及其在肿瘤研究中的应用进展[J].重庆医科大学学报,2025,50(1):6-13. DOI: 10.13406/j.cnki.cyxb.003639.
Huang Yiwei,Xiang Tingxiu,Liu Xinghe,et al.Imaging mass cytometry technology and its application in tumor research[J].Journal of Chongqing Medical University,2025,50(1):6-13. DOI: 10.13406/j.cnki.cyxb.003639.
多重单细胞蛋白组技术已成为生物医学研究的热点,其中质谱流式成像(imaging mass cytometry,IMC)彻底解决了荧光基团间严重的串色问题,并弥补了单细胞测序技术缺失的组织空间信息。该技术能够在单张组织切片上同时标记数十种靶标,并在单细胞层面获得它们的表达水平及细胞定位,进行深度的细胞表型原位分析并从时间和空间水平直观描绘出单细胞蛋白组图谱,因其独特的技术优势逐渐成为肿瘤研究领域新兴的强有力工具。本文将详细介绍IMC的技术原理,并通过分析近期应用案例阐述其在细胞表型鉴定、生物标志物检测、肿瘤免疫调节判定、肿瘤异质性区分、临床预后指导及反应预测等肿瘤研究方面的应用进展,推动肿瘤空间组学与现有技术的进一步结合。
Multiplex single-cel
l proteomics technology has become a hot topic in biomedical research,among which imaging mass cytometry(IMC) completely solves the serious problem of cross-color between fluorophores and makes up for the lack of tissue spatial information in single-cell sequencing technology. This technique can label dozens of targets simultaneously on a single tissue section,obtain their expression levels and cell localization at the single-cell level,perform in-depth cell phenotypic
in situ
analysis,and visually depict single-cell proteome maps from the temporal and spatial levels,and due to its unique technical advantages,it has become a powerful tool in the field of tumor research. This article elaborates on the technical principle of IMC and summarizes the advances in the application of IMC in cell phenotype identification,biomarker detection,tumor immunomodulatory determination,tumor heterogeneity differentiation,clinical prognosis guidance,and response prediction by analyzing recent cases,so as to promote the further integration of tumor spatial omics with existing technologies.
Schreiber RD , Old LJ , Smyth MJ . Cancer immunoediting:integrating immunity’s roles in cancer suppression and promotion [J ] . Science , 2011 , 331 ( 6024 ): 1565 - 1570 .
Topalian SL , Hodi FS , Brahmer JR , et al . Safety,activity,and immune correlates of anti-PD-1 antibody in cancer [J ] . N Engl J Med , 2012 , 366 ( 26 ): 2443 - 2454 .
Chang Q , Ornatsky OI , Siddiqui I , et al . Imaging mass cytometry [J ] . Cytometry A , 2017 , 91 ( 2 ): 160 - 169 .
Gohil SH , Iorgulescu JB , Braun DA , et al . Applying high-dimensional single-cell technologies to the analysis of cancer immunotherapy [J ] . Nat Rev Clin Oncol , 2021 , 18 ( 4 ): 244 - 256 .
Cotechini T , Jones O , Hindmarch CCT . Imaging mass cytometry in immuno-oncology [M ] // The Tumor Microenvironment . New York : Humana , 2023 : 1 - 15 .
Giesen C , Wang HA , Schapiro D , et al . Highly multiplexed imaging of tumor tissues with subcellular resolution by mass cytometry [J ] . Nat Methods , 2014 , 11 ( 4 ): 417 - 422 .
Glasson Y , Chépeaux LA , Dumé AS , et al . Single-cell high-dimensional imaging mass cytometry:one step beyond in oncology [J ] . Semin Immunopathol , 2023 , 45 ( 1 ): 17 - 28 .
Han GJ , Chen SY , Gonzalez VD , et al . Atomic mass tag of bismuth-209 for increasing the immunoassay multiplexing capacity of mass cytometry [J ] . Cytometry A , 2017 , 91 ( 12 ): 1150 - 1163 .
Gerdtsson E , Pore M , Thiele JA , et al . Multiplex protein detection on circulating tumor cells from liquid biopsies using imaging mass cytometry [J ] . Converg Sci Phys Oncol , 2018 , 4 ( 1 ): 015002 .
Allo B , Lou XD , Bouzekri A , et al . Clickable and high-sensitivity metal-containing tags for mass cytometry [J ] . Bioconjug Chem , 2018 , 29 ( 6 ): 2028 - 2038 .
Rovira-Clavé X , Jiang SZ , Bai YH , et al . Subcellular localization of biomolecules and drug distribution by high-definition ion beam imaging [J ] . Nat Commun , 2021 , 12 ( 1 ): 4628 .
Catena R , Montuenga LM , Bodenmiller B . Ruthenium counterstaining for imaging mass cytometry [J ] . J Pathol , 2018 , 244 ( 4 ): 479 - 484 .
Ijsselsteijn ME , van der Breggen R , Farina Sarasqueta A , et al . A 40-marker panel for high dimensional characterization of cancer immune microenvironments by imaging mass cytometry [J ] . Front Immunol , 2019 , 10 : 2534 .
Baars MJD , Sinha N , Amini M , et al . MATISSE:a method for improved single cell segmentation in imaging mass cytometry [J ] . BMC Biol , 2021 , 19 ( 1 ): 99 .
Hoch T , Schulz D , Eling N , et al . Multiplexed imaging mass cytometry of the chemokine milieus in melanoma characterizes features of the response to immunotherapy [J ] . Sci Immunol , 2022 , 7 ( 70 ): eabk1692 .
Baharlou H , Canete NP , Cunningham AL , et al . Mass cytometry imaging for the study of human diseases-applications and data analysis strategies [J ] . Front Immunol , 2019 , 10 : 2657 .
Chang Q , Ornatsky OI , Siddiqui I , et al . Biodistribution of cisplatin revealed by imaging mass cytometry identifies extensive collagen binding in tumor and normal tissues [J ] . Sci Rep , 2016 , 6 : 36641 .
Carpenter AE , Jones TR , Lamprecht MR , et al . CellProfiler:image analysis software for identifying and quantifying cell phenotypes [J ] . Genome Biol , 2006 , 7 ( 10 ): R100 .
Schapiro D , Jackson HW , Raghuraman S , et al . histoCAT:analysis of cell phenotypes and interactions in multiplex image cytometry data [J ] . Nat Methods , 2017 , 14 ( 9 ): 873 - 876 .
Fischer JR , Jackson HW , de Souza N , et al . Multiplex imaging of breast cancer lymph node metastases identifies prognostic single-cell populations independent of clinical classifiers [J ] . Cell Rep Med , 2023 , 4 ( 3 ): 100977 .
Jackson HW , Fischer JR , Zanotelli VRT , et al . The single-cell pathology landscape of breast cancer [J ] . Nature , 2020 , 578 ( 7796 ): 615 - 620 .
Yi QJ , Wang J , Liu TT , et al . scRNA-Seq and imaging mass cytometry analyses unveil iNKT cells-mediated anti-tumor immunity in pancreatic cancer liver metastasis [J ] . Cancer Lett , 2023 , 561 : 216149 .
Mi QS , Dimitrion P , Hamzavi I , et al . Dysregulated CD38 expression in blood and skin immune cells of patients with hidradenitis suppurativa [J/OL ] . Res Sq , 2023 [ epub ahead of print ] . doi: 10.21203/rs.3.rs-2609421/v1 http://dx.doi.org/10.21203/rs.3.rs-2609421/v1 .
Ravi VM , Will P , Kueckelhaus J , et al . Spatially resolved multi-omics deciphers bidirectional tumor-host interdependence in glioblastoma [J ] . Cancer Cell , 2022 , 40 ( 6 ): 639 - 655 .
Funingana IG , Bedia JS , Huang YW , et al . Multiparameter single-cell proteomic technologies give new insights into the biology of ovarian tumors [J ] . Semin Immunopathol , 2023 , 45 ( 1 ): 43 - 59 .
Krop J , van der Meeren LE , van der Hoorn MP , et al . Identification of a unique intervillous cellular signature in chronic histiocytic intervillositis [J ] . Placenta , 2023 , 139 : 34 - 42 .
Le Rochais M , Hémon P , Ben-Guigui D , et al . Deciphering the maturation of tertiary lymphoid structures in cancer and inflammatory diseases of the digestive tract using imaging mass cytometry [J ] . Front Immunol , 2023 , 14 : 1147480 .
Roelands J , van der Ploeg M , Ijsselsteijn ME , et al . Transcriptomic and immunophenotypic profiling reveals molecular and immunological hallmarks of colorectal cancer tumourigenesis [J ] . Gut , 2023 , 72 ( 7 ): 1326 - 1339 .
Sorin M , Karimi E , Rezanejad M , et al . Single-cell spatial landscape of immunotherapy response reveals mechanisms of CXCL13 enhanced antitumor immunity [J ] . J Immunother Cancer , 2023 , 11 ( 2 ): e005545 .
Wang XQ , Danenberg E , Huang CS , et al . Spatial predictors of immunotherapy response in triple-negative breast cancer [J ] . Nature , 2023 , 621 ( 7980 ): 868 - 876 .
Sanmamed MF , Nie XX , Desai SS , et al . A burned-out CD8 + T-cell subset expands in the tumor microenvironment and curbs cancer immunotherapy [J ] . Cancer Discov , 2021 , 11 ( 7 ): 1700 - 1715 .
Xiang HD , Ramil CP , Hai J , et al . Cancer-associated fibroblasts promote immunosuppression by inducing ROS-generating monocytic MDSCs in lung squamous cell carcinoma [J ] . Cancer Immunol Res , 2020 , 8 ( 4 ): 436 - 450 .
van Dam S , Baars MJD , Vercoulen Y . Multiplex tissue imaging:spatial Revelations in the tumor microenvironment [J ] . Cancers , 2022 , 14 ( 13 ): 3170 .
Karimi E , Yu MW , Maritan SM , et al . Single-cell spatial immune landscapes of primary and metastatic brain tumours [J ] . Nature , 2023 , 614 ( 7948 ): 555 - 563 .
Rahim MK , Okholm TLH , Jones KB , et al . Dynamic CD8 + Tcell responses to cancer immunotherapy in human regional lymph nodes are disrupted in metastatic lymph nodes [J ] . Cell , 2023 , 186 ( 6 ): 1127 - 1143 .
Apollonio B , Spada F , Petrov N , et al . Tumor-activated lymph node fibroblasts suppress T cell function in diffuse large B cell lymphoma [J ] . J Clin Invest , 2023 , 133 ( 13 ): e166070 .
Mancino C , Pasto A , de Rosa E , et al . Immunomodulatory biomimetic nanoparticles target articular cartilage trauma after systemic administration [J ] . Heliyon , 2023 , 9 ( 6 ): e16640 .
Heiland DH , Ravi VM , Will P , et al . Spatiotemporal heterogeneity of glioblastoma is dictated by microenvironmental interference [J ] . Brain Spine , 2021 , 1 : 100550 .
Lin QY , Zhou YQ , Ma J , et al . Single-cell analysis reveals the multiple patterns of immune escape in the nasopharyngeal carcinoma microenvironment [J ] . Clin Transl Med , 2023 , 13 ( 6 ): e1315 .
Danielli SG , Porpiglia E , De Micheli AJ , et al . Single-cell profiling of alveolar rhabdomyosarcoma reveals RAS pathway inhibitors as cell-fate hijackers with therapeutic relevance [J ] . Sci Adv , 2023 , 9 ( 6 ): eade9238 .
Yao LY , He FN , Zhao QY , et al . Spatial multiplexed protein profiling of cardiac ischemia-reperfusion injury [J ] . Circ Res , 2023 , 133 ( 1 ): 86 - 103 .
He JZ , Chen Y , Zeng FM , et al . Spatial analysis of stromal signatures identifies invasive front carcinoma-associated fibroblasts as suppressors of anti-tumor immune response in esophageal cancer [J ] . J Exp Clin Cancer Res , 2023 , 42 ( 1 ): 136 .
Robert M , Chépeaux LA , Glasson Y , et al . Comprehensive analysis of cell lineages involved in giant cell arteritis pathogenesis using highly multiplexed imaging mass cytometry [J ] . Autoimmun Rev , 2023 , 22 ( 1 ): 103216 .
Zabransky DJ , Danilova L , Leatherman JM , et al . Profiling of syngeneic mouse HCC tumor models as a framework to understand anti-PD-1 sensitive tumor microenvironments [J ] . Hepatology , 2023 , 77 ( 5 ): 1566 - 1579 .
Eng J , Bucher E , Hu Z , et al . Robust biomarker discovery through multiplatform multiplex image analysis of breast cancer clinical cohorts [J/OL ] . bioRxiv , 2023 [ epub ahead of print ] . doi: 10.1101/2023.01.31.525753 http://dx.doi.org/10.1101/2023.01.31.525753 .
Chen J , Amoozgar Z , Liu X , et al . Reprogramming intrahepatic cholangiocarcinoma immune microenvironment by chemotherapy and CTLA-4 blockade enhances anti-PD1 therapy [J/OL ] . bioRxiv , 2023 [ epub ahead of print ] . doi: 10.1101/2023.01.26.525680 http://dx.doi.org/10.1101/2023.01.26.525680 .
Sorin M , Rezanejad M , Karimi E , et al . Single-cell spatial landscapes of the lung tumour immune microenvironment [J ] . Nature , 2023 , 614 ( 7948 ): 548 - 554 .
Wang V , Liu ZC , Martinek J , et al . Computational immune synapse analysis reveals T-cell interactions in distinct tumor microenvironments [J/OL ] . Res Sq , 2023 [ epub ahead of print ] . doi: 10.21203/rs.3.rs-2968528/v1 http://dx.doi.org/10.21203/rs.3.rs-2968528/v1 .
Cao YS , Chang Q , Cabanero M , et al . Tumor platinum concentrations and pathological responses following cisplatin-containing chemotherapy in gastric cancer patients [J ] . J Gastrointest Cancer , 2019 , 50 ( 4 ): 801 - 807 .
Cao YS , Chang Q , Zhang WJ , et al . Skin platinum deposition in colorectal cancer patients following oxaliplatin-based therapy [J ] . Cancer Chemother Pharmacol , 2019 , 84 ( 6 ): 1195 - 1200 .
Sayin K , Üngördü A . Investigation of anticancer properties of caffeinated complexes via computational chemistry methods [J ] . Spectrochim Acta A Mol Biomol Spectrosc , 2018 , 193 : 147 - 155 .
Lau JKC , Deubel DV . Hydrolysis of the anticancer drug cisplatin:pitfalls in the interpretation of quantum chemical calculations [J ] . J Chem Theory Comput , 2006 , 2 ( 1 ): 103 - 106 .
Alvarado-Soto L , Ramirez-Tagle R . A theoretical study of the binding of[Re₆Se₈(OH)₂(H₂O)₄]rhenium clusters to DNA purine base guanine [J ] . Materials , 2015 , 8 ( 7 ): 3938 - 3944 .
Deo C , Abdelfattah AS , Bhargava HK , et al . The HaloTag as a general scaffold for far-red tunable chemigenetic indicators [J ] . Nat Chem Biol , 2021 , 17 ( 6 ): 718 - 723 .
Duncan RR , Bergmann A , Cousin MA , et al . Multi-dimensional time-correlated single photon counting(TCSPC) fluorescence lifetime imaging microscopy(FLIM) to detect FRET in cells [J ] . J Microsc , 2004 , 215 ( Pt 1 ): 1 - 12 .
Dang JQ , Li HX , Zhang LL , et al . New Structure Mass Tag based on Zr-NMOF for Multiparameter and Sensitive Single-Cell Interrogating in Mass Cytometry [J ] . Adv Mater , 2021 , 33 ( 35 ): e2008297 .
Ptacek J , Locke D , Finck R , et al . Multiplexed ion beam imaging(MIBI) for characterization of the tumor microenvironment across tumor types [J ] . Lab Invest , 2020 , 100 ( 8 ): 1111 - 1123 .
Keren L , Bosse M , Thompson S , et al . MIBI-TOF:a multiplexed imaging platform relates cellular phenotypes and tissue structure [J ] . Sci Adv , 2019 , 5 ( 10 ): eaax5851 .
Parrot D , Papazian S , Foil D , et al . Imaging the unimaginable:desorption electrospray ionization-imaging mass spectrometry(DESI-IMS) in natural product research [J ] . Planta Med , 2018 , 84 ( 9/10 ): 584 - 593 .
0
浏览量
10
下载量
0
CSCD
关联资源
相关文章
相关作者
相关机构
京公网安备11010802024621