技术背景
2022年空间多组学技术被Nature评为七大“颠覆性”技术之一,是将基因组、转录组、蛋白质组以及代谢组的检测结果与组织原位信息相结合,重塑空间立体结构内相关组学信息的定位分布情况。随着多个免疫治疗药物的获批,肿瘤免疫疗法日趋成熟,人们越来越多地关注组织微环境的概念及其在肿瘤免疫治疗中的作用。肿瘤细胞可以通过释放细胞外信号影响周边的微环境,促进肿瘤血管增生和抑制周边的免疫细胞,而肿瘤微环境中的免疫细胞及因子又可以影响肿瘤细胞的生长(见下图)。

服务内容
空间多组学技术众多,从高通量空间转录组和蛋白组到低通量RNA原位检测技术和多重荧光免疫组化技术,不同方法学在各自应用领域发挥着独特的作用。菲诺维康拥有完整的空间多组学平台,集研发、实验室服务以及临床应用开发于一体,提供多组学(DNA\RNA\蛋白)一站式空间生物学解决方案。

应用方向

案例展示
空间表型分析可以将标记物组合(panel)分为几大类:鉴别T细胞及其亚型(如杀伤性T细胞、辅助型T细胞)在肿瘤中的分布;鉴别M1型/M2型巨噬细胞在肿瘤中的分布;聚焦B细胞不同亚型(如CD20,CD21为代表的B细胞亚型)以及三级淋巴结构在肿瘤中的分布;关注更多种免疫细胞类型,如将NK细胞、树突细胞引入到panel中,观察不同免疫细胞在肿瘤中的分布;聚焦结合肿瘤标记物以及免疫检测点,观察不同几大细胞类型(肿瘤细胞、B细胞、T细胞、巨噬细胞等)在肿瘤中的分布。

人肠癌组织

人乳腺癌组织

人黑色素瘤组织

人肺癌组织
参考文献
- Lu S, Stein JE, Rimm DL, et al. Comparison of Biomarker Modalities for Predicting Response to PD-1/PD-L1 Checkpoint Blockade: A Systematic Review and Meta-analysis. JAMA Oncol. 2019;5(8):1195-1204. doi:10.1001/jamaoncol.2019.1549.
- Gao J, Navai N, Alhalabi O, et al. Neoadjuvant PD-L1 plus CTLA-4 blockade in patients with cisplatin-ineligible operable high-risk urothelial carcinoma. Nat Med. 2020 Dec;26(12):1845-1851. doi: 10.1038/s41591-020-1086-y. Epub 2020 Oct 12.
- Park, Y.H., Lal, S., Lee, J.E. et al. Chemotherapy induces dynamic immune responses in breast cancers that impact treatment outcome. Nat Commun. 2020 Dec 2;11(1):6175.doi: 10.1038/s41467-020-19933-0.
- Biswas S, Mandal G, Payne KK, et al. IgA transcytosis and antigen recognition govern ovarian cancer immunity. Nature. 2021 Mar;591(7850):464-470. doi: 10.1038/s41586-020-03144-0. Epub 2021 Feb 3. PMID: 33536615.
- Berry S, Giraldo NA, Green BF, et al. Analysis of multispectral imaging with the AstroPath platform informs efficacy of PD-1 blockade. Science. 2021 Jun 11;372(6547):eaba2609. doi: 10.1126/science.aba2609. PMID: 34112666.
- Hoyt CC. Multiplex Immunofluorescence and Multispectral Imaging: Forming the Basis of a Clinical Test Platform for Immuno-Oncology. Front Mol Biosci. 2021 Jun 2;8:674747. doi: 10.3389/fmolb.2021.674747.
- Taube JM, Roman K, Engle EL, et al. Multi-institutional TSA-amplified Multiplexed Immunofluorescence Reproducibility Evaluation (MITRE) Study. J Immunother Cancer. 2021 Jul;9(7):e002197. doi: 10.1136/jitc-2020-002197.
- Vanhersecke L, Brunet M, Guégan JP, et al. Mature tertiary lymphoid structures predict immune checkpoint inhibitor efficacy in solid tumors independently of PD-L1 expression. Nat Cancer. 2021 Aug;2(8):794-802. doi: 10.1038/s43018-021-00232-6. Epub 2021 Aug 12.
- Anadon CM, Yu X, Hänggi K, et al. Ovarian cancer immunogenicity is governed by a narrow subset of progenitor tissue-resident memory T cells. Cancer Cell. 2022 May 9;40(5):545-557.e13. doi: 10.1016/j.ccell.2022.03.008. Epub 2022 Apr 14.
- Attrill GH, Owen CN, Ahmed T, et al. Higher proportions of CD39+ tumor-resident cytotoxic T cells predict recurrence-free survival in patients with stage III melanoma treated with adjuvant immunotherapy. J Immunother Cancer. 2022 Jun;10(6):e004771. doi: 10.1136/jitc-2022-004771.
- Melero I, Villalba-Esparza M, Recalde-Zamacona B, et al. Neutrophil Extracellular Traps, Local IL-8 Expression, and Cytotoxic T-Lymphocyte Response in the Lungs of Patients With Fatal COVID-19. Chest. 2022 Nov;162(5):1006-1016. doi: 10.1016/j.chest.2022.06.007. Epub 2022 Jun 15.
- Liu Z, Zhao Y, Kong P, et al. Integrated multi-omics profiling yields a clinically relevant molecular classification for esophageal squamous cell carcinoma. Cancer Cell. 2023 Jan 9;41(1):181-195.e9. doi: 10.1016/j.ccell.2022.12.004. Epub 2022 Dec 29.
- Yang S, Qian L, Li Z, et al. Integrated Multi-Omics Landscape of Liver Metastases. Gastroenterology. 2023 Mar;164(3):407-423.e17. doi: 10.1053/j.gastro.2022.11.029. Epub 2022 Nov 26.