A Single-cell Tumor Immune Atlas for Precision Oncology

Overview

Journal Genome Res

Specialty Genetics

Date 2021 Sep 22

PMID 34548323

Citations 75

Authors

Paula Nieto

Marc Elosua-Bayes

Juan L Trincado

Domenica Marchese

Ramon Massoni-Badosa

Maria Salvany

Ana Henriques

Juan Nieto

Sergio Aguilar-Fernandez

Elisabetta Mereu

Catia Moutinho

Sara Ruiz

Patricia Lorden

Vanessa T Chin

Dominik Kaczorowski

Chia-Ling Chan

Richard Gallagher

Angela Chou

Ester Planas-Rigol

Carlota Rubio-Perez

Ivo Gut

Josep M Piulats

Joan Seoane

Joseph E Powell

Eduard Batlle

Holger Heyn

Affiliations

Soon will be listed here.

Abstract

The tumor immune microenvironment is a main contributor to cancer progression and a promising therapeutic target for oncology. However, immune microenvironments vary profoundly between patients, and biomarkers for prognosis and treatment response lack precision. A comprehensive compendium of tumor immune cells is required to pinpoint predictive cellular states and their spatial localization. We generated a single-cell tumor immune atlas, jointly analyzing published data sets of >500,000 cells from 217 patients and 13 cancer types, providing the basis for a patient stratification based on immune cell compositions. Projecting immune cells from external tumors onto the atlas facilitated an automated cell annotation system. To enable in situ mapping of immune populations for digital pathology, we applied SPOTlight, combining single-cell and spatial transcriptomics data and identifying colocalization patterns of immune, stromal, and cancer cells in tumor sections. We expect the tumor immune cell atlas, together with our versatile toolbox for precision oncology, to advance currently applied stratification approaches for prognosis and immunotherapy.

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References

Regev A, Teichmann S, Lander E, Amit I, Benoist C, Birney E . The Human Cell Atlas. Elife. 2017; 6. PMC: 5762154. DOI: 10.7554/eLife.27041. View

Stahl P, Salmen F, Vickovic S, Lundmark A, Fernandez Navarro J, Magnusson J . Visualization and analysis of gene expression in tissue sections by spatial transcriptomics. Science. 2016; 353(6294):78-82. DOI: 10.1126/science.aaf2403. View

Yost K, Satpathy A, Wells D, Qi Y, Wang C, Kageyama R . Clonal replacement of tumor-specific T cells following PD-1 blockade. Nat Med. 2019; 25(8):1251-1259. PMC: 6689255. DOI: 10.1038/s41591-019-0522-3. View

Li H, van der Leun A, Yofe I, Lubling Y, Gelbard-Solodkin D, van Akkooi A . Dysfunctional CD8 T Cells Form a Proliferative, Dynamically Regulated Compartment within Human Melanoma. Cell. 2019; 176(4):775-789.e18. PMC: 7253294. DOI: 10.1016/j.cell.2018.11.043. View

Zhang Q, He Y, Luo N, Patel S, Han Y, Gao R . Landscape and Dynamics of Single Immune Cells in Hepatocellular Carcinoma. Cell. 2019; 179(4):829-845.e20. DOI: 10.1016/j.cell.2019.10.003. View

Calon A, Lonardo E, Berenguer-Llergo A, Espinet E, Hernando-Momblona X, Iglesias M . Stromal gene expression defines poor-prognosis subtypes in colorectal cancer. Nat Genet. 2015; 47(4):320-9. DOI: 10.1038/ng.3225. View

Lee H, Hong Y, Etlioglu H, Cho Y, Pomella V, Van den Bosch B . Lineage-dependent gene expression programs influence the immune landscape of colorectal cancer. Nat Genet. 2020; 52(6):594-603. DOI: 10.1038/s41588-020-0636-z. View

Lavin Y, Kobayashi S, Leader A, Amir E, Elefant N, Bigenwald C . Innate Immune Landscape in Early Lung Adenocarcinoma by Paired Single-Cell Analyses. Cell. 2017; 169(4):750-765.e17. PMC: 5737939. DOI: 10.1016/j.cell.2017.04.014. View

Park J, Botting R, Conde C, Popescu D, Lavaert M, Kunz D . A cell atlas of human thymic development defines T cell repertoire formation. Science. 2020; 367(6480). PMC: 7611066. DOI: 10.1126/science.aay3224. View

10.

Peng J, Sun B, Chen C, Zhou J, Chen Y, Chen H . Single-cell RNA-seq highlights intra-tumoral heterogeneity and malignant progression in pancreatic ductal adenocarcinoma. Cell Res. 2019; 29(9):725-738. PMC: 6796938. DOI: 10.1038/s41422-019-0195-y. View

11.

Wu T, Madireddi S, de Almeida P, Banchereau R, Chen Y, Chitre A . Peripheral T cell expansion predicts tumour infiltration and clinical response. Nature. 2020; 579(7798):274-278. DOI: 10.1038/s41586-020-2056-8. View

12.

Popescu D, Botting R, Stephenson E, Green K, Webb S, Jardine L . Decoding human fetal liver haematopoiesis. Nature. 2019; 574(7778):365-371. PMC: 6861135. DOI: 10.1038/s41586-019-1652-y. View

13.

Asp M, Giacomello S, Larsson L, Wu C, Furth D, Qian X . A Spatiotemporal Organ-Wide Gene Expression and Cell Atlas of the Developing Human Heart. Cell. 2019; 179(7):1647-1660.e19. DOI: 10.1016/j.cell.2019.11.025. View

14.

Elosua-Bayes M, Nieto P, Mereu E, Gut I, Heyn H . SPOTlight: seeded NMF regression to deconvolute spatial transcriptomics spots with single-cell transcriptomes. Nucleic Acids Res. 2021; 49(9):e50. PMC: 8136778. DOI: 10.1093/nar/gkab043. View

15.

Rodriques S, Stickels R, Goeva A, Martin C, Murray E, Vanderburg C . Slide-seq: A scalable technology for measuring genome-wide expression at high spatial resolution. Science. 2019; 363(6434):1463-1467. PMC: 6927209. DOI: 10.1126/science.aaw1219. View

16.

Guinney J, Dienstmann R, Wang X, De Reynies A, Schlicker A, Soneson C . The consensus molecular subtypes of colorectal cancer. Nat Med. 2015; 21(11):1350-6. PMC: 4636487. DOI: 10.1038/nm.3967. View

17.

Sade-Feldman M, Yizhak K, Bjorgaard S, Ray J, de Boer C, Jenkins R . Defining T Cell States Associated with Response to Checkpoint Immunotherapy in Melanoma. Cell. 2018; 175(4):998-1013.e20. PMC: 6641984. DOI: 10.1016/j.cell.2018.10.038. View

18.

Alashwal H, El Halaby M, Crouse J, Abdalla A, Moustafa A . The Application of Unsupervised Clustering Methods to Alzheimer's Disease. Front Comput Neurosci. 2019; 13:31. PMC: 6543980. DOI: 10.3389/fncom.2019.00031. View

19.

Salzer M, Lafzi A, Berenguer-Llergo A, Youssif C, Castellanos A, Solanas G . Identity Noise and Adipogenic Traits Characterize Dermal Fibroblast Aging. Cell. 2018; 175(6):1575-1590.e22. DOI: 10.1016/j.cell.2018.10.012. View

20.

Vieira Braga F, Kar G, Berg M, Carpaij O, Polanski K, Simon L . A cellular census of human lungs identifies novel cell states in health and in asthma. Nat Med. 2019; 25(7):1153-1163. DOI: 10.1038/s41591-019-0468-5. View