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Applying high-dimensional single-cell technologies to the analysis of cancer immunotherapy

Abstract

Advances in molecular biology, microfluidics and bioinformatics have empowered the study of thousands or even millions of individual cells from malignant tumours at the single-cell level of resolution. This high-dimensional, multi-faceted characterization of the genomic, transcriptomic, epigenomic and proteomic features of the tumour and/or the associated immune and stromal cells enables the dissection of tumour heterogeneity, the complex interactions between tumour cells and their microenvironment, and the details of the evolutionary trajectory of each tumour. Single-cell transcriptomics, the ability to track individual T cell clones through paired sequencing of the T cell receptor genes and high-dimensional single-cell spatial analysis are all areas of particular relevance to immuno-oncology. Multidimensional biomarker signatures will increasingly be crucial to guiding clinical decision-making in each patient with cancer. High-dimensional single-cell technologies are likely to provide the resolution and richness of data required to generate such clinically relevant signatures in immuno-oncology. In this Perspective, we describe advances made using transformative single-cell analysis technologies, especially in relation to clinical response and resistance to immunotherapy, and discuss the growing utility of single-cell approaches for answering important research questions.

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Fig. 1: Workflow for single-cell analysis in immuno-oncology.
Fig. 2: General biospecimen framework for incorporating single-cell analyses in clinical trials involving immunotherapies.

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Acknowledgements

The work of S.H.G. is supported by a Kay Kendall Leukaemia Fund Fellowship. The work of J.B.I. is supported by the NCI (K12CA090354) and Conquer Cancer Foundation-Sontag Foundation Young Investigator Award. The work of D.A.B. is supported by the DF/HCC Kidney Cancer SPORE Career Enhancement Program (P50CA101942-15), DOD CDMRP (KC170216, KC190130) and the DOD Academy of Kidney Cancer Investigators (KC190128). The work of D.B.K. is supported by the NIH/NCI (R21 CA216772-01A1 and NCI-SPORE-2P50CA101942-11A1). The work of K.J.L. is supported by the NIH/NCI (U24 CA224331 R01CA229261-01, NIH/NCI P01CA229092) and the NIH/NIAID (U19 AI082630).

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All authors researched data for this manuscript. D.B.K., S.H.G., J.B.I. and D.A.B. made substantial contributions to discussions of content. All authors wrote the manuscript and reviewed and/or edited the manuscript prior to submission.

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Correspondence to Kenneth J. Livak.

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D.A.B. has received non-financial support from Bristol Myers Squibb, honoraria from LM Education/Exchange Services and personal fees from Adept Field Solutions, Blueprint Partnerships, Charles River Associates, Dedham Group, Defined Health, Insight Strategy, Octane Global, Slingshot Insights and Trinity Group. D.B.K. has acted as an advisor of and has received consulting fees from Neon Therapeutics and owns equity in Aduro Biotech, Agenus, Armata Pharmaceuticals, Breakbio, BioMarin Pharmaceutical, Bristol Myers Squibb, Celldex Therapeutics, Editas Medicine, Exelixis, Gilead Sciences, IMV, Lexicon Pharmaceuticals, Moderna, Regeneron Pharmaceuticals and Stemline Therapeutics. The other authors declare no competing interests.

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Gohil, S.H., Iorgulescu, J.B., Braun, D.A. et al. Applying high-dimensional single-cell technologies to the analysis of cancer immunotherapy. Nat Rev Clin Oncol 18, 244–256 (2021). https://doi.org/10.1038/s41571-020-00449-x

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