The T cell differentiation landscape is shaped by tumour mutations in lung cancer.
Journal
Nature cancer
ISSN: 2662-1347
Titre abrégé: Nat Cancer
Pays: England
ID NLM: 101761119
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
entrez:
18
8
2020
pubmed:
18
8
2020
medline:
18
8
2020
Statut:
ppublish
Résumé
Tumour mutational burden (TMB) predicts immunotherapy outcome in non-small cell lung cancer (NSCLC), consistent with immune recognition of tumour neoantigens. However, persistent antigen exposure is detrimental for T cell function. How TMB affects CD4 and CD8 T cell differentiation in untreated tumours, and whether this affects patient outcomes is unknown. Here we paired high-dimensional flow cytometry, exome, single-cell and bulk RNA sequencing from patients with resected, untreated NSCLC to examine these relationships. TMB was associated with compartment-wide T cell differentiation skewing, characterized by loss of TCF7-expressing progenitor-like CD4 T cells, and an increased abundance of dysfunctional CD8 and CD4 T cell subsets, with significant phenotypic and transcriptional similarity to neoantigen-reactive CD8 T cells. A gene signature of redistribution from progenitor-like to dysfunctional states associated with poor survival in lung and other cancer cohorts. Single-cell characterization of these populations informs potential strategies for therapeutic manipulation in NSCLC.
Identifiants
pubmed: 32803172
doi: 10.1038/s43018-020-0066-y
pmc: PMC7115931
mid: EMS86680
pii: 10.1038/s43018-020-0066-y
doi:
Substances chimiques
B7-H1 Antigen
0
Biomarkers, Tumor
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Pagination
546-561Subventions
Organisme : Medical Research Council
ID : FC001169
Pays : United Kingdom
Organisme : European Research Council
ID : 617844
Pays : International
Organisme : Cancer Research UK
ID : A20465
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P014712/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M009033/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 211179/Z/18/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : FC001202
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P014712/2
Pays : United Kingdom
Organisme : Cancer Research UK
ID : A22246
Pays : United Kingdom
Investigateurs
Charles Swanton
(C)
Mariam Jamal-Hanjani
(M)
Karl S Peggs
(KS)
Andrew Georgiou
(A)
Mariana Werner Sunderland
(MW)
James L Reading
(JL)
Sergio A Quezada
(SA)
Ehsan Ghorani
(E)
Marc Robert de Massy
(MR)
David A Moore
(DA)
Allan Hackshaw
(A)
Nicholas McGranahan
(N)
Rachel Rosenthal
(R)
Selvaraju Veeriah
(S)
Dhruva Biswas
(D)
Crispin T Hiley
(CT)
Benny Chain
(B)
Gareth A Wilson
(GA)
Nicolai J Birkbak
(NJ)
Maise Al Bakir
(MA)
Kevin Litchfield
(K)
Javier Herrero
(J)
Roberto Salgado
(R)
Yenting Ngai
(Y)
Abigail Sharp
(A)
Cristina Rodrigues
(C)
Oliver Pressey
(O)
Sean Smith
(S)
Nicole Gower
(N)
Harjot Dhanda
(H)
David Lawrence
(D)
Martin Hayward
(M)
Nikolaos Panagiotopoulos
(N)
Robert George
(R)
Davide Patrini
(D)
Mary Falzon
(M)
Elaine Borg
(E)
Reena Khiroya
(R)
Asia Ahmed
(A)
Magali Taylor
(M)
Junaid Choudhary
(J)
Penny Shaw
(P)
Sam M Janes
(SM)
Martin Forster
(M)
Tanya Ahmad
(T)
Siow Ming Lee
(SM)
Dawn Carnell
(D)
Ruheena Mendes
(R)
Jeremy George
(J)
Neal Navani
(N)
Marco Scarci
(M)
Elisa Bertoja
(E)
Robert C M Stephens
(RCM)
Emilie Martinoni Hoogenboom
(EM)
James W Holding
(JW)
Steve Bandula
(S)
Thomas B K Watkins
(TBK)
Mickael Escudero
(M)
Aengus Stewart
(A)
Andrew Rowan
(A)
Jacki Goldman
(J)
Peter Van Loo
(P)
Richard Kevin Stone
(RK)
Tamara Denner
(T)
Emma Nye
(E)
Sophia Ward
(S)
Emilia L Lim
(EL)
Stefan Boeing
(S)
Maria Greco
(M)
Jerome Nicod
(J)
Clare Puttick
(C)
Katey Enfield
(K)
Emma Colliver
(E)
Brittany Campbell
(B)
Christopher Abbosh
(C)
Yin Wu
(Y)
Marcin Skrzypski
(M)
Robert E Hynds
(RE)
Teresa Marafioti
(T)
John A Hartley
(JA)
Pat Gorman
(P)
Helen L Lowe
(HL)
Leah Ensell
(L)
Victoria Spanswick
(V)
Angeliki Karamani
(A)
Maryam Razaq
(M)
Stephan Beck
(S)
Ariana Huebner
(A)
Michelle Dietzen
(M)
Cristina Naceur-Lombardelli
(C)
Mita Afroza Akther
(MA)
Haoran Zhai
(H)
Nnennaya Kannu
(N)
Elizabeth Manzano
(E)
Supreet Kaur Bola
(SK)
Elena Hoxha
(E)
Emine Hatipoglu
(E)
Stephanie Ogwuru
(S)
Gillian Price
(G)
Sylvie Dubois-Marshall
(S)
Keith Kerr
(K)
Shirley Palmer
(S)
Heather Cheyne
(H)
Joy Miller
(J)
Keith Buchan
(K)
Mahendran Chetty
(M)
Mohammed Khalil
(M)
Veni Ezhil
(V)
Vineet Prakash
(V)
Girija Anand
(G)
Sajid Khan
(S)
Kelvin Lau
(K)
Michael Sheaff
(M)
Peter Schmid
(P)
Louise Lim
(L)
John Conibear
(J)
Roland Schwarz
(R)
Jonathan Tugwood
(J)
Jackie Pierce
(J)
Caroline Dive
(C)
Ged Brady
(G)
Dominic G Rothwell
(DG)
Francesca Chemi
(F)
Elaine Kilgour
(E)
Fiona Blackhall
(F)
Lynsey Priest
(L)
Matthew G Krebs
(MG)
Philip Crosbie
(P)
John Le Quesne
(J)
Joan Riley
(J)
Lindsay Primrose
(L)
Luke Martinson
(L)
Nicolas Carey
(N)
Jacqui A Shaw
(JA)
Dean Fennell
(D)
Apostolos Nakas
(A)
Sridhar Rathinam
(S)
Louise Nelson
(L)
Kim Ryanna
(K)
Mohamad Tuffail
(M)
Amrita Bajaj
(A)
Fiona Morgan
(F)
Malgorzata Kornaszewska
(M)
Richard Attanoos
(R)
Haydn Adams
(H)
Helen Davies
(H)
Mathew Carter
(M)
C R Lindsay
(CR)
Fabio Gomes
(F)
Zoltan Szallasi
(Z)
Istvan Csabai
(I)
Miklos Diossy
(M)
Hugo Aerts
(H)
Alan Kirk
(A)
Mo Asif
(M)
John Butler
(J)
Rocco Bilanca
(R)
Nikos Kostoulas
(N)
Mairead MacKenzie
(M)
Maggie Wilcox
(M)
Sara Busacca
(S)
Alan Dawson
(A)
Mark R Lovett
(MR)
Michael Shackcloth
(M)
Sarah Feeney
(S)
Julius Asante-Siaw
(J)
John Gosney
(J)
Angela Leek
(A)
Nicola Totten
(N)
Jack Davies Hodgkinson
(JD)
Rachael Waddington
(R)
Jane Rogan
(J)
Katrina Moore
(K)
William Monteiro
(W)
Hilary Marshall
(H)
Kevin G Blyth
(KG)
Craig Dick
(C)
Andrew Kidd
(A)
Eric Lim
(E)
Paulo De Sousa
(P)
Simon Jordan
(S)
Alexandra Rice
(A)
Hilgardt Raubenheimer
(H)
Harshil Bhayani
(H)
Morag Hamilton
(M)
Lyn Ambrose
(L)
Anand Devaraj
(A)
Hema Chavan
(H)
Sofina Begum
(S)
Aleksander Mani
(A)
Daniel Kaniu
(D)
Mpho Malima
(M)
Sarah Booth
(S)
Andrew G Nicholson
(AG)
Nadia Fernandes
(N)
Jessica E Wallen
(JE)
Pratibha Shah
(P)
Sarah Danson
(S)
Jonathan Bury
(J)
John Edwards
(J)
Jennifer Hill
(J)
Sue Matthews
(S)
Yota Kitsanta
(Y)
Jagan Rao
(J)
Sara Tenconi
(S)
Laura Socci
(L)
Kim Suvarna
(K)
Faith Kibutu
(F)
Patricia Fisher
(P)
Robin Young
(R)
Joann Barker
(J)
Fiona Taylor
(F)
Kirsty Lloyd
(K)
Teresa Light
(T)
Tracey Horey
(T)
Dionysis Papadatos-Pastos
(D)
Peter Russell
(P)
Sara Lock
(S)
Kayleigh Gilbert
(K)
Babu Naidu
(B)
Gerald Langman
(G)
Andrew Robinson
(A)
Hollie Bancroft
(H)
Amy Kerr
(A)
Salma Kadiri
(S)
Charlotte Ferris
(C)
Gary Middleton
(G)
Madava Djearaman
(M)
Akshay Patel
(A)
Christian Ottensmeier
(C)
Serena Chee
(S)
Benjamin Johnson
(B)
Aiman Alzetani
(A)
Emily Shaw
(E)
Jason Lester
(J)
Yvonne Summers
(Y)
Raffaele Califano
(R)
Paul Taylor
(P)
Rajesh Shah
(R)
Piotr Krysiak
(P)
Kendadai Rammohan
(K)
Eustace Fontaine
(E)
Richard Booton
(R)
Matthew Evison
(M)
Stuart Moss
(S)
Juliette Novasio
(J)
Leena Joseph
(L)
Paul Bishop
(P)
Anshuman Chaturvedi
(A)
Helen Doran
(H)
Felice Granato
(F)
Vijay Joshi
(V)
Elaine Smith
(E)
Angeles Montero
(A)
Déclaration de conflit d'intérêts
Competing interest statement S.A.Q., K.S.P. and C.S. are co-founders of Achilles Therapeutics. C.S. receives grant support from Pfizer, AstraZeneca, BMS, Roche-Ventana and Boehringer-Ingelheim. C.S. has consulted for Pfizer, Novartis, GlaxoSmithKline, MSD, BMS, Celgene, AstraZeneca, Illumina, Genentech, Roche-Ventana, GRAIL, Medicxi, and the Sarah Cannon Research Institute. C.S. is a shareholder of Apogen Biotechnologies, Epic Bioscience, GRAIL, and has stock options in and is co-founder of Achilles Therapeutics. R.R., N.M. and G.A.W. have stock options in and have consulted for Achilles Therapeutics. J.L.R and M.A.B have consulted for Achilles Therapeutics. P.D.B and M.W.S are employees of Achilles Therapeutics.
Références
Schumacher, T. N. & Schreiber, R. D. Neoantigens in cancer immunotherapy. Science 348, 69–74 (2015).
pubmed: 25838375
doi: 10.1126/science.aaa4971
Rizvi, N. A. et al. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 348, 124–128 (2015).
pubmed: 25765070
pmcid: 4993154
Mcgranahan, N. et al. Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science 351, 1463–1469 (2016).
pubmed: 26940869
pmcid: 4984254
doi: 10.1126/science.aaf1490
Gros, A. et al. Prospective identification of neoantigen-specific lymphocytes in the peripheral blood of melanoma patients. Nat. Med. 22, 433–438 (2016).
pubmed: 26901407
pmcid: 7446107
doi: 10.1038/nm.4051
Van Allen, E. M. et al. Genomic correlates of response to CTLA-4 blockade in metastatic melanoma. Science 350, 207–211 (2015).
pubmed: 26359337
pmcid: 5054517
doi: 10.1126/science.aad0095
Snyder, A. et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N. Engl. J. Med. 371, 2189–2199 (2014).
pubmed: 25409260
pmcid: 4315319
Thommen, D. S. & Schumacher, T. N. T cell dysfunction in cancer. Cancer Cell 33, 547–562 (2018).
pubmed: 29634943
pmcid: 7116508
doi: 10.1016/j.ccell.2018.03.012
Reading, J. L. et al. The function and dysfunction of memory CD8
pubmed: 29664561
doi: 10.1111/imr.12657
Zinkernagel, R. M. et al. Antigen localisation regulates immune responses in a dose- and time-dependent fashion: a geographical view of immune reactivity. Immunol. Rev. 156, 199–209 (1997).
pubmed: 9176709
doi: 10.1111/j.1600-065X.1997.tb00969.x
Rolland, M. et al. Recognition of HIV-1 peptides by host CTL is related to HIV-1 similarity to human proteins. PLoS ONE 2, e823 (2007).
pubmed: 17786195
pmcid: 1952107
doi: 10.1371/journal.pone.0000823
Neefjes, J. & Ovaa, H. A peptide’s perspective on antigen presentation to the immune system. Nat. Chem. Biol. 9, 769–775 (2013).
pubmed: 24231618
doi: 10.1038/nchembio.1391
Kaech, S. M. & Wherry, E. J. Heterogeneity and cell-fate decisions in effector and memory CD8
pubmed: 17892848
pmcid: 3431921
doi: 10.1016/j.immuni.2007.08.007
Kaufmann, D. E. et al. Upregulation of CTLA-4 by HIV-specific CD4
pubmed: 17906628
doi: 10.1038/ni1515
Day, C. L. et al. PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression. Nature 443, 350–354 (2006).
pubmed: 16921384
doi: 10.1038/nature05115
Han, S., Asoyan, A., Rabenstein, H., Nakano, N. & Obst, R. Role of antigen persistence and dose for CD4
pubmed: 21059929
doi: 10.1073/pnas.1008437107
pmcid: 2996637
Wherry, E. J. & Kurachi, M. Molecular and cellular insights into T cell exhaustion. Nat. Rev. Immunol. 15, 486–499 (2015).
pubmed: 26205583
pmcid: 4889009
doi: 10.1038/nri3862
Philip, M. & Schietinger, A. Heterogeneity and fate choice: T cell exhaustion in cancer and chronic infections. Curr. Opin. Immunol. 58, 98–103 (2019).
pubmed: 31181510
pmcid: 7608527
doi: 10.1016/j.coi.2019.04.014
Kallies, A., Zehn, D. & Utzschneider, D. T. Precursor exhausted T cells: key to successful immunotherapy? Nat. Rev. Immunol. 20, 128–136 (2020).
pubmed: 31591533
doi: 10.1038/s41577-019-0223-7
Crawford, A. et al. Molecular and transcriptional basis of CD4
pubmed: 24530057
pmcid: 3990591
doi: 10.1016/j.immuni.2014.01.005
Fletcher, J. M. et al. Cytomegalovirus-specific CD4
pubmed: 16339561
doi: 10.4049/jimmunol.175.12.8218
Palmer, P. E., Boritz, E. & Wilson, C. C. Effects of sustained HIV-1 plasma viremia on HIV-1 Gag-specific CD4
pubmed: 14978142
doi: 10.4049/jimmunol.172.5.3337
Patil, V. S. et al. Precursors of human CD4
pubmed: 29352091
pmcid: 5931334
doi: 10.1126/sciimmunol.aan8664
Di Mitri, D. et al. Reversible senescence in human CD4
pubmed: 21788446
doi: 10.4049/jimmunol.1100978
Sade-Feldman, M. et al. Defining T cell states associated with response to checkpoint immunotherapy in melanoma. Cell 175, 998–1013.e20 (2018).
pubmed: 30388456
pmcid: 6641984
doi: 10.1016/j.cell.2018.10.038
Miller, B. C. et al. Subsets of exhausted CD8
pubmed: 30778252
pmcid: 6673650
doi: 10.1038/s41590-019-0312-6
Utzschneider, D. T. et al. T cell factor 1-expressing memory-like CD8
pubmed: 27533016
doi: 10.1016/j.immuni.2016.07.021
Siddiqui, I. et al. Intratumoral Tcf1
pubmed: 30635237
doi: 10.1016/j.immuni.2018.12.021
Im, S. J. et al. Defining CD8
pubmed: 27501248
pmcid: 5297183
doi: 10.1038/nature19330
Smith, C. M. et al. Cognate CD4
pubmed: 15475958
doi: 10.1038/ni1129
Matloubian, M., Concepcion, R. J. & Ahmed, R. CD4
pubmed: 7966595
pmcid: 237269
doi: 10.1128/jvi.68.12.8056-8063.1994
Schietinger, A., Philip, M., Liu, R. B., Schreiber, K. & Schreiber, H. Bystander killing of cancer requires the cooperation of CD4
pubmed: 20921286
pmcid: 2964573
doi: 10.1084/jem.20092450
Sahin, U. et al. Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer. Nature 547, 222–226 (2017).
pubmed: 28678784
doi: 10.1038/nature23003
Tran, E. et al. Cancer immunotherapy based on mutation-specific CD4
pubmed: 24812403
pmcid: 6686185
doi: 10.1126/science.1251102
Jamal-Hanjani, M. et al. Tracking the evolution of non-small-cell lung cancer. N. Engl. J. Med. 376, 2109–2121 (2017).
pubmed: 28445112
doi: 10.1056/NEJMoa1616288
Becht, E. et al. Dimensionality reduction for visualizing single-cell data using UMAP. Nat. Biotechnol. 37, 38–44 (2018).
doi: 10.1038/nbt.4314
Thommen, D. S. et al. A transcriptionally and functionally distinct PD-1
pubmed: 29892065
pmcid: 6110381
doi: 10.1038/s41591-018-0057-z
Brenchley, J. M. et al. Expression of CD57 defines replicative senescence and antigen-induced apoptotic death of CD8
pubmed: 12433688
doi: 10.1182/blood-2002-07-2103
Simoni, Y. et al. Bystander CD8
pubmed: 29769722
doi: 10.1038/s41586-018-0130-2
Schietinger, A. et al. Tumor-specific T cell dysfunction is a dynamic antigen-driven differentiation program initiated early during tumorigenesis. Immunity 45, 389–401 (2016).
pubmed: 27521269
pmcid: 5119632
doi: 10.1016/j.immuni.2016.07.011
Simonetta, F. et al. High eomesodermin expression among CD57
pubmed: 25100841
pmcid: 4178742
doi: 10.1128/JVI.02013-14
Li, H. et al. Dysfunctional CD8 T cells form a proliferative, dynamically regulated compartment within human melanoma. Cell 176, 775–789.e18 (2019).
pubmed: 30595452
doi: 10.1016/j.cell.2018.11.043
Guo, X. et al. Global characterization of T cells in non-small-cell lung cancer by single-cell sequencing. Nat. Med. 24, 978–985 (2018).
pubmed: 29942094
doi: 10.1038/s41591-018-0045-3
Gros, A. et al. PD-1 identifies the patient-specific CD8
pubmed: 24667641
pmcid: 4001555
doi: 10.1172/JCI73639
Okoye, A. et al. Progressive CD4
pubmed: 17724130
pmcid: 2118701
doi: 10.1084/jem.20070567
Joshi, K. et al. Spatial heterogeneity of the T cell receptor repertoire reflects the mutational landscape in lung cancer. Nat. Med. 25, 1549–1559 (2019).
pubmed: 31591606
pmcid: 6890490
doi: 10.1038/s41591-019-0592-2
Baitsch, L. et al. Exhaustion of tumor-specific CD8
pubmed: 21555851
pmcid: 3104769
doi: 10.1172/JCI46102
Wherry, E. J. et al. Molecular signature of CD8
pubmed: 17950003
doi: 10.1016/j.immuni.2007.09.006
Shin, B. et al. Effector CD4 T cells with progenitor potential mediate chronic intestinal inflammation. J. Exp. Med. 215, 1803–1812 (2018).
pubmed: 29915024
pmcid: 6028516
doi: 10.1084/jem.20172335
Tilstra, J. S. et al. Kidney-infiltrating T cells in murine lupus nephritis are metabolically and functionally exhausted. J. Clin. Invest. 128, 4884–4897 (2018).
pubmed: 30130253
pmcid: 6205402
doi: 10.1172/JCI120859
Liston, A. et al. Inhibition of CCR6 function reduces the severity of experimental autoimmune encephalomyelitis via effects on the priming phase of the immune response. J. Immunol. 182, 3121–3130 (2009).
pubmed: 19234209
doi: 10.4049/jimmunol.0713169
Scott, A. C. et al. TOX is a critical regulator of tumour-specific T cell differentiation. Nature 571, 270–274 (2019).
pubmed: 31207604
pmcid: 7698992
doi: 10.1038/s41586-019-1324-y
Hombrink, P. et al. Programs for the persistence, vigilance and control of human CD8
pubmed: 27776108
doi: 10.1038/ni.3589
Thommen, D. S. et al. Progression of lung cancer is associated with increased dysfunction of T cells defined by coexpression of multiple inhibitory receptors. Cancer Immunol. Res. 3, 1344–1355 (2015).
pubmed: 26253731
doi: 10.1158/2326-6066.CIR-15-0097
Philip, M. et al. Chromatin states define tumour-specific T cell dysfunction and reprogramming. Nature 545, 452–456 (2017).
pubmed: 28514453
pmcid: 5693219
doi: 10.1038/nature22367
Efremova, M., Vento-Tormo, M., Teichmann, S. A. & Vento-Tormo, R. CellPhoneDB: inferring cell–cell communication from combined expression of multi-subunit ligand–receptor complexes. Nat. Protoc. 15, 1484–1506 (2020).
pubmed: 32103204
doi: 10.1038/s41596-020-0292-x
Xing, S. et al. Tcf1 and Lef1 transcription factors establish CD8
pubmed: 27111144
pmcid: 4873337
doi: 10.1038/ni.3456
Duhen, T. et al. Co-expression of CD39 and CD103 identifies tumor-reactive CD8 T cells in human solid tumors. Nat. Commun. 9, 2724 (2018).
pubmed: 30006565
pmcid: 6045647
doi: 10.1038/s41467-018-05072-0
Brummelman, J. et al. High-dimensional single cell analysis identifies stem-like cytotoxic CD8
pubmed: 30154266
pmcid: 6170179
doi: 10.1084/jem.20180684
He, Y. et al. MHC class II expression in lung cancer. Lung Cancer 112, 75–80 (2017).
pubmed: 29191604
doi: 10.1016/j.lungcan.2017.07.030
Gejman, R. S. et al. Rejection of immunogenic tumor clones is limited by clonal fraction. eLife 7, e41090 (2018).
pubmed: 30499773
pmcid: 6269121
doi: 10.7554/eLife.41090
Roth, A. et al. PyClone: statistical inference of clonal population structure in cancer. Nat. Methods 11, 396–398 (2014).
pubmed: 24633410
pmcid: 4864026
doi: 10.1038/nmeth.2883
Hendry, S. et al. Assessing tumor-infiltrating lymphocytes in solid tumors. Adv. Anat. Pathol. 24, 311–335 (2017).
pubmed: 28777143
pmcid: 5638696
doi: 10.1097/PAP.0000000000000161
Denkert, C. et al. Standardized evaluation of tumor-infiltrating lymphocytes in breast cancer: results of the ring studies of the international immuno-oncology biomarker working group. Mod. Pathol. 29, 1155–1164 (2016).
pubmed: 27363491
doi: 10.1038/modpathol.2016.109
Thorsson, V. et al. The immune landscape of cancer. Immunity 48, 812–830.e14 (2018).
pubmed: 29628290
pmcid: 5982584
doi: 10.1016/j.immuni.2018.03.023
Liu, J. et al. An integrated TCGA pan-cancer clinical data resource to drive high-quality survival outcome analytics. Cell 173, 400–416.e11 (2018).
pubmed: 29625055
pmcid: 6066282
doi: 10.1016/j.cell.2018.02.052
Ellrott, K. et al. Scalable open science approach for mutation calling of tumor exomes using multiple genomic pipelines. Cell Syst. 6, 271–281.e7 (2018).
pubmed: 29596782
pmcid: 6075717
doi: 10.1016/j.cels.2018.03.002
Nowicka, M. et al. CyTOF workflow: differential discovery in high-throughput high-dimensional cytometry datasets. F1000Res. 6, 748 (2017).
pubmed: 28663787
doi: 10.12688/f1000research.11622.1
Van Gassen, S. et al. FlowSOM: using self-organizing maps for visualization and interpretation of cytometry data. Cytom. A 87, 636–645 (2015).
doi: 10.1002/cyto.a.22625
Ahmadzadeh, M. et al. Tumor-infiltrating human CD4
pubmed: 30635355
pmcid: 6685542
doi: 10.1126/sciimmunol.aao4310
Lun, A. T. L., Richard, A. C. & Marioni, J. C. Testing for differential abundance in mass cytometry data. Nat. Methods 14, 707–709 (2017).
pubmed: 28504682
pmcid: 6155493
doi: 10.1038/nmeth.4295
Weber, L. M. & Robinson, M. D. Comparison of clustering methods for high-dimensional single-cell flow and mass cytometry data. Cytom. A 89, 1084–1096 (2016).
doi: 10.1002/cyto.a.23030
Rosenthal, R. et al. Neoantigen-directed immune escape in lung cancer evolution. Nature 567, 479–485 (2019).
pubmed: 30894752
pmcid: 6954100
doi: 10.1038/s41586-019-1032-7
Using C1 to Generate Single-Cell cDNA Libraries for mRNA Sequencing Protocol PN 100-7168 M1 (Fluidigm, 2018).
Li, W. V. & Li, J. J. An accurate and robust imputation method scImpute for single-cell RNA-Seq data. Nat. Commun. 9, 997 (2018).
pubmed: 29520097
pmcid: 5843666
doi: 10.1038/s41467-018-03405-7
Oetjen, K. A. et al. Human bone marrow assessment by single-cell RNA sequencing, mass cytometry, and flow cytometry. JCI Insight 3, 124928 (2018).
pubmed: 30518681
doi: 10.1172/jci.insight.124928
Soneson, C. & Robinson, M. D. Bias, robustness and scalability in single-cell differential expression analysis. Nat. Methods 15, 255–261 (2018).
pubmed: 29481549
doi: 10.1038/nmeth.4612
Waugh, K. A. et al. Molecular profile of tumor-specific CD8
pubmed: 27371726
doi: 10.4049/jimmunol.1600589
Godec, J. et al. Compendium of immune signatures identifies conserved and species-specific biology in response to inflammation. Immunity 44, 194–206 (2016).
pubmed: 26795250
pmcid: 5330663
doi: 10.1016/j.immuni.2015.12.006
Charoentong, P. et al. Pan-cancer immunogenomic analyses reveal genotype–immunophenotype relationships and predictors of response to checkpoint blockade. Cell Rep. 18, 248–262 (2017).
pubmed: 28052254
doi: 10.1016/j.celrep.2016.12.019
Danaher, P. et al. Gene expression markers of tumor infiltrating leukocytes. J. Immunother. Cancer 5, 18 (2017).
pubmed: 28239471
pmcid: 5319024
doi: 10.1186/s40425-017-0215-8
Aran, D., Hu, Z. & Butte, A. J. xCell: digitally portraying the tissue cellular heterogeneity landscape. Genome Biol. 18, 220 (2017).
pubmed: 29141660
pmcid: 5688663
doi: 10.1186/s13059-017-1349-1
Bindea, G. et al. Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer. Immunity 39, 782–795 (2013).
Zheng, C. et al. Landscape of infiltrating T cells in liver cancer revealed by single-cell sequencing. Cell 169, 1342–1356.e16 (2017).