High-throughput Single-сell Sequencing in Cancer Research

Overview

Journal Signal Transduct Target Ther

Specialties Cell Biology
Pharmacology

Date 2022 May 3

PMID 35504878

Authors

Qingzhu Jia

Han Chu

Zheng Jin

Haixia Long

Bo Zhu

Affiliations

Soon will be listed here.

Abstract

With advances in sequencing and instrument technology, bioinformatics analysis is being applied to batches of massive cells at single-cell resolution. High-throughput single-cell sequencing can be utilized for multi-omics characterization of tumor cells, stromal cells or infiltrated immune cells to evaluate tumor progression, responses to environmental perturbations, heterogeneous composition of the tumor microenvironment, and complex intercellular interactions between these factors. Particularly, single-cell sequencing of T cell receptors, alone or in combination with single-cell RNA sequencing, is useful in the fields of tumor immunology and immunotherapy. Clinical insights obtained from single-cell analysis are critically important for exploring the biomarkers of disease progression or antitumor treatment, as well as for guiding precise clinical decision-making for patients with malignant tumors. In this review, we summarize the clinical applications of single-cell sequencing in the fields of tumor cell evolution, tumor immunology, and tumor immunotherapy. Additionally, we analyze the tumor cell response to antitumor treatment, heterogeneity of the tumor microenvironment, and response or resistance to immune checkpoint immunotherapy. The limitations of single-cell analysis in cancer research are also discussed.

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References

Jia Q, Wu W, Wang Y, Alexander P, Sun C, Gong Z . Local mutational diversity drives intratumoral immune heterogeneity in non-small cell lung cancer. Nat Commun. 2018; 9(1):5361. PMC: 6299138. DOI: 10.1038/s41467-018-07767-w. View

Pilkington E, Suys E, Trevaskis N, Wheatley A, Zukancic D, Algarni A . From influenza to COVID-19: Lipid nanoparticle mRNA vaccines at the frontiers of infectious diseases. Acta Biomater. 2021; 131:16-40. PMC: 8272596. DOI: 10.1016/j.actbio.2021.06.023. View

Gerlinger M, Rowan A, Horswell S, Math M, Larkin J, Endesfelder D . Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med. 2012; 366(10):883-892. PMC: 4878653. DOI: 10.1056/NEJMoa1113205. View

Cavalli F, Remke M, Rampasek L, Peacock J, Shih D, Luu B . Intertumoral Heterogeneity within Medulloblastoma Subgroups. Cancer Cell. 2017; 31(6):737-754.e6. PMC: 6163053. DOI: 10.1016/j.ccell.2017.05.005. View

Navin N, Hicks J . Future medical applications of single-cell sequencing in cancer. Genome Med. 2011; 3(5):31. PMC: 3219072. DOI: 10.1186/gm247. View

Tang F, Barbacioru C, Wang Y, Nordman E, Lee C, Xu N . mRNA-Seq whole-transcriptome analysis of a single cell. Nat Methods. 2009; 6(5):377-82. DOI: 10.1038/nmeth.1315. View

Buenrostro J, Wu B, Litzenburger U, Ruff D, Gonzales M, Snyder M . Single-cell chromatin accessibility reveals principles of regulatory variation. Nature. 2015; 523(7561):486-90. PMC: 4685948. DOI: 10.1038/nature14590. View

Bandura D, Baranov V, Ornatsky O, Antonov A, Kinach R, Lou X . Mass cytometry: technique for real time single cell multitarget immunoassay based on inductively coupled plasma time-of-flight mass spectrometry. Anal Chem. 2009; 81(16):6813-22. DOI: 10.1021/ac901049w. View

Vitak S, Torkenczy K, Rosenkrantz J, Fields A, Christiansen L, Wong M . Sequencing thousands of single-cell genomes with combinatorial indexing. Nat Methods. 2017; 14(3):302-308. PMC: 5908213. DOI: 10.1038/nmeth.4154. View

10.

Rosenberg A, Roco C, Muscat R, Kuchina A, Sample P, Yao Z . Single-cell profiling of the developing mouse brain and spinal cord with split-pool barcoding. Science. 2018; 360(6385):176-182. PMC: 7643870. DOI: 10.1126/science.aam8999. View

11.

Guo F, Li L, Li J, Wu X, Hu B, Zhu P . Single-cell multi-omics sequencing of mouse early embryos and embryonic stem cells. Cell Res. 2017; 27(8):967-988. PMC: 5539349. DOI: 10.1038/cr.2017.82. View

12.

Sandberg R . Entering the era of single-cell transcriptomics in biology and medicine. Nat Methods. 2014; 11(1):22-4. DOI: 10.1038/nmeth.2764. View

13.

Zhu C, Preissl S, Ren B . Single-cell multimodal omics: the power of many. Nat Methods. 2020; 17(1):11-14. DOI: 10.1038/s41592-019-0691-5. View

14.

Wang L, Mo S, Li X, He Y, Yang J . Single-cell RNA-seq reveals the immune escape and drug resistance mechanisms of mantle cell lymphoma. Cancer Biol Med. 2020; 17(3):726-739. PMC: 7476085. DOI: 10.20892/j.issn.2095-3941.2020.0073. View

15.

de Miguel M, Calvo E . Clinical Challenges of Immune Checkpoint Inhibitors. Cancer Cell. 2020; 38(3):326-333. DOI: 10.1016/j.ccell.2020.07.004. View

16.

Triana S, Vonficht D, Jopp-Saile L, Raffel S, Lutz R, Leonce D . Single-cell proteo-genomic reference maps of the hematopoietic system enable the purification and massive profiling of precisely defined cell states. Nat Immunol. 2021; 22(12):1577-1589. PMC: 8642243. DOI: 10.1038/s41590-021-01059-0. View

17.

Gulati G, Sikandar S, Wesche D, Manjunath A, Bharadwaj A, Berger M . Single-cell transcriptional diversity is a hallmark of developmental potential. Science. 2020; 367(6476):405-411. PMC: 7694873. DOI: 10.1126/science.aax0249. View

18.

La Manno G, Soldatov R, Zeisel A, Braun E, Hochgerner H, Petukhov V . RNA velocity of single cells. Nature. 2018; 560(7719):494-498. PMC: 6130801. DOI: 10.1038/s41586-018-0414-6. View

19.

Jin S, Guerrero-Juarez C, Zhang L, Chang I, Ramos R, Kuan C . Inference and analysis of cell-cell communication using CellChat. Nat Commun. 2021; 12(1):1088. PMC: 7889871. DOI: 10.1038/s41467-021-21246-9. View

20.

Efremova M, Vento-Tormo M, Teichmann S, Vento-Tormo R . CellPhoneDB: inferring cell-cell communication from combined expression of multi-subunit ligand-receptor complexes. Nat Protoc. 2020; 15(4):1484-1506. DOI: 10.1038/s41596-020-0292-x. View