Innate Immune Landscape in Early Lung Adenocarcinoma by Paired Single-Cell Analyses
Open accessAbstract
To guide the design of immunotherapy strategies for patients with early stage lung tumors, we developed a multiscale immune profiling strategy to map the immune landscape of early lung adenocarcinoma lesions to search for tumor-driven immune changes. Utilizing a barcoding method that allows a simultaneous single-cell analysis of the tumor, non-involved lung, and blood cells, we provide a detailed immune cell atlas of early lung tumors. We show that stage I lung adenocarcinoma lesions already harbor significantly altered T cell and NK cell compartments. Moreover, we identified changes in tumor-infiltrating myeloid cell (TIM) subsets that likely compromise anti-tumor T cell immunity. Paired single-cell analyses thus offer valuable knowledge of tumor-driven immune changes, providing a powerful tool for the rational design of immune therapies. VIDEO ABSTRACT.
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TREM2+ macrophages have been reported in tumors.
“TREM2+ macrophages have also been reported in tumors (Lavin et al., 2017; Song et al., 2019), but the impact of TREM2 in tumor immune responses has not been addressed.”
From TREM2 Modulation Remodels the Tumor Myeloid Landscape Enhancing Anti-PD-1 Immunotherapy (2020) · cites this paper as Lavin et al., 2017
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ggplot2: Elegant Graphics for Data Analysis
Wickham, H. (2009) · doi:10.1007/978-0-387-98141-3 · Cited by 14,447 · see citing works
Gene Expression Omnibus: NCBI gene expression and hybridization array data repository
Edgar, R. (2002) · Nucleic Acids Research · doi:10.1093/nar/30.1.207 · Cited by 13,288 · see citing works
Reduced Lung-Cancer Mortality with Low-Dose Computed Tomographic Screening
The National Lung Screening Trial Research Team (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1102873 · Cited by 11,064 · see citing works
Merad, M., Sathe, P., Helft, J., Miller, J., & Mortha, A. (2013) · Annual Review of Immunology · doi:10.1146/annurev-immunol-020711-074950 · Cited by 2,309 · see citing works
Hildner, K., Edelson, B. T., Purtha, W. E., Diamond, M., Matsushita, H., Kohyama, M., Calderon, B., Schraml, B. U., Unanue, E. R., Diamond, M. S., et al. (2008) · Science · doi:10.1126/science.1164206 · Cited by 2,081 · see citing works
Monocytes and macrophages: developmental pathways and tissue homeostasis
Ginhoux, F., & Jung, S. (2014) · Nature Reviews Immunology · doi:10.1038/nri3671 · Cited by 1,840 · see citing works
Amir, E.-A. D., Davis, K. L., Tadmor, M. D., Simonds, E. F., Levine, J. H., Bendall, S. C., Shenfeld, D. K., Krishnaswamy, S., Nolan, G. P., & Pe'er, D. (2013) · Nature Biotechnology · doi:10.1038/nbt.2594 · Cited by 1,550 · see citing works
Self-citationGermain, C., Gnjatic, S., Tamzalit, F., Knockaert, S., Remark, R., Goc, J., Lepelley, A., Becht, E., Katsahian, S., Bizouard, G., et al. (2014) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201309-1611oc · Cited by 833 · see citing works
Self-citationTREM-2 promotes macrophage survival and lung disease after respiratory viral infection
Wu, K., Byers, D. E., Jin, X., Agapov, E., Alexander-Brett, J., Patel, A. C., Cella, M., Gilfilan, S., Colonna, M., Kober, D. L., et al. (2015) · Journal of Experimental Medicine · doi:10.1084/jem.20141732 · Cited by 207 · see citing works
Flagged first, then by citations
Research works printed but not linked: 56
- Besse B Johnson M Janne PA Janne PA Garassino MC Eberhardt WE Peters S Toh CK Kurata T Li Z 2015 16LBA Phase II, single-arm trial (BIRCH) of atezolizumab as first-line or subsequent therapy for locally advanced or metastatic PD-L1-selected non-small cell lung cancer (NSCLC) European Journal of Cancer 51
- Black WC Keeler EB Soneji SS 2015 Cost-effectiveness of CT screening in the National Lung Screening Trial N Engl J Med 372 388 25607437
- Blondel VD Guillaume J-L Lambiotte R Lefebvre E 2008 Fast unfolding of communities in large networks Journal of statistical mechanics: theory and experiment 2008 P10008
- Broz ML Binnewies M Boldajipour B Nelson AE Pollack JL Erle DJ Barczak A Rosenblum MD Daud A Barber DL 2014 Dissecting the tumor myeloid compartment reveals rare activating antigen-presenting cells critical for T cell immunity Cancer cell 26 638 652 25446897 PMC4254577
- Carlson CS Emerson RO Sherwood AM Desmarais C Chung M-W Parsons JM Steen MS LaMadrid-Herrmannsfeldt MA Williamson DW Livingston RJ 2013 Using synthetic templates to design an unbiased multiplex PCR assay Nature Communications 4 2680 24157944
- Chang Q Bournazou E Sansone P Berishaj M Gao SP Daly L Wels J Theilen T Granitto S Zhang X 2013 The IL-6/JAK/Stat3 Feed-Forward Loop Drives Tumorigenesis and Metastasis Neoplasia 15 848 IN845 23814496 PMC3689247
- Chen JJ Yao PL Yuan A Hong TM Shun CT Kuo ML Lee YC Yang PC 2003 Up-regulation of tumor interleukin-8 expression by infiltrating macrophages: its correlation with tumor angiogenesis and patient survival in non-small cell lung cancer Clin Cancer Res 9 12576442
- Chen TJ Kotecha N 2014 Cytobank: providing an analytics platform for community cytometry data analysis and collaboration High-Dimensional Single Cell Analysis (Springer) 127 157 24590675
- Desch AN Gibbings SL Goyal R Kolde R Bednarek J Bruno T Slansky JE Jacobelli J Mason R Ito Y 2016 Flow Cytometric Analysis of Mononuclear Phagocytes in Nondiseased Human Lung and Lung-Draining Lymph Nodes Am J Respir Crit Care Med 193 614 626 26551758 PMC4824940
- Dieu-Nosjean MC Antoine M Danel C Heudes D Wislez M Poulot V Rabbe N Laurans L Tartour E de Chaisemartin L 2008 Long-term survival for patients with non-small-cell lung cancer with intratumoral lymphoid structures J Clin Oncol 26 4410 4417 18802153
- Dutertre CA Wang LF Ginhoux F 2014 Aligning bona fide dendritic cell populations across species Cell Immunol 291 3 10 25262488
- Engblom C Pfirschke C Pittet MJ 2016 The role of myeloid cells in cancer therapies Nat Rev Cancer 16 447 462 27339708
- Fehrenbacher L Spira A Ballinger M Kowanetz M Vansteenkiste J Mazieres J Park K Smith D Artal-Cortes A Lewanski C 2016 Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial Lancet 387 1837 1846 26970723
- Gabrilovich DI Ostrand-Rosenberg S Bronte V 2012 Coordinated regulation of myeloid cells by tumours Nat Rev Immunol 12 253 268 22437938 PMC3587148
- Goc J Germain C Vo-Bourgais TK Lupo A Klein C Knockaert S de Chaisemartin L Ouakrim H Becht E Alifano M 2014 Dendritic cells in tumor-associated tertiary lymphoid structures signal a Th1 cytotoxic immune contexture and license the positive prognostic value of infiltrating CD8+ T cells Cancer Res 74 705 715 24366885
- Goldstraw P Chansky K Crowley J Rami-Porta R Asamura H Eberhardt WEE Nicholson AG Groome P Mitchell A Bolejack V 2016 The IASLC Lung Cancer Staging Project: Proposals for Revision of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for Lung Cancer Journal of Thoracic Oncology 11 39 51 26762738
- Haniffa M Collin M Ginhoux F 2013 Ontogeny and functional specialization of dendritic cells in human and mouse Adv Immunol 120 1 49 24070379
- Hanna RN Cekic C Sag D Tacke R Thomas GD Nowyhed H Herrley E Rasquinha N McArdle S Wu R 2015 Patrolling monocytes control tumor metastasis to the lung Science 350 985 990 26494174 PMC4869713
- Herbst RS Soria JC Kowanetz M Fine GD Hamid O Gordon MS Sosman JA McDermott DF Powderly JD Gettinger SN 2014 Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients Nature 515 563 567 25428504 PMC4836193
- Jaitin DA Kenigsberg E Keren-Shaul H Elefant N Paul F Zaretsky I Mildner A Cohen N Jung S Tanay A 2014 Massively parallel single-cell RNA-seq for marker-free decomposition of tissues into cell types Science 343 776 779 24531970 PMC4412462
- Joshi NS Akama-Garren EH Lu Y Lee DY Chang GP Li A DuPage M Tammela T Kerper NR Farago AF 2015 Regulatory T Cells in Tumor-Associated Tertiary Lymphoid Structures Suppress Anti-tumor T Cell Responses Immunity 43 579 590 26341400 PMC4826619
- Kirsch I Vignali M Robins H 2015 T-cell receptor profiling in cancer Mol Oncol 9 2063 2070 26404496 PMC5528728
- Lavin Y Merad M 2013 Macrophages: Gatekeepers of Tissue Integrity Cancer Immunology Research 1 201 209 24777851 PMC4144820
- Lavin Y Winter D Blecher-Gonen R David E Keren-Shaul H Merad M Jung S Amit I 2014 Tissue-Resident Macrophage Enhancer Landscapes Are Shaped by the Local Microenvironment Cell 159 1312 1326 25480296 PMC4437213
- Levine JH Simonds EF Bendall SC Davis KL Amir E-A Tadmor MD Litvin O Fienberg HG Jager A Zunder ER 2015 Data-Driven Phenotypic Dissection of AML Reveals Progenitor-like Cells that Correlate with Prognosis Cell 162 184 197 26095251 PMC4508757
- Moussion C Girard JP 2011 Dendritic cells control lymphocyte entry to lymph nodes through high endothelial venules Nature 479 542 546 22080953
- Naidoo J Wang X Woo KM Iyriboz T Halpenny D Cunningham J Chaft JE Segal NH Callahan MK Lesokhin AM Pneumonitis in Patients Treated With Anti–Programmed Death-1/Programmed Death Ligand 1 Therapy Journal of Clinical Oncology 0 JCO.2016.2068.2005 PMC5559901 27646942
- Nishino M Giobbie-Hurder A Hatabu H Ramaiya NH Hodi F 2016 Incidence of programmed cell death 1 inhibitor–related pneumonitis in patients with advanced cancer: A systematic review and meta-analysis JAMA Oncology 2 1607 1616 27540850
- Paul F Arkin Ya Giladi A Jaitin DA Kenigsberg E Keren-Shaul H Winter D Lara-Astiaso D Gury M Weiner A 2015 Transcriptional heterogeneity and lineage commitment in myeloid progenitors Cell 163 1663 1677 26627738
- Pham CT 2006 Neutrophil serine proteases: specific regulators of inflammation Nat Rev Immunol 6 541 550 16799473
- Pignon JP Tribodet H Scagliotti GV Douillard JY Shepherd FA Stephens RJ Dunant A Torri V Rosell R Seymour L 2008 Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group J Clin Oncol 26 3552 3559 18506026
- Pitzalis C Jones GW Bombardieri M Jones SA 2014 Ectopic lymphoid-like structures in infection, cancer and autoimmunity Nat Rev Immunol 14 447 462 24948366
- Qian B-Z Li J Zhang H Kitamura T Zhang J Campion LR Kaiser EA Snyder LA Pollard JW 2011 CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis Nature 475 222 225 21654748 PMC3208506
- Reddy RC 2008 Immunomodulatory Role of PPAR-γ in Alveolar Macrophages Journal of Investigative Medicine 56 522 527 18317435
- Remark R Merghoub T Grabe N Litjens G Damotte D Wolchok JD Merad M Gnjatic S 2016 In-depth tissue profiling using multiplexed immunohistochemical consecutive staining on single slide Science Immunology 1 aaf6925 28783673 PMC10152404
- Ricote M Li AC Willson TM Kelly CJ Glass CK 1998 The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation Nature 391 79 82 9422508
- Ritchie ME Phipson B Wu D Hu Y Law CW Shi W Smyth GK 2015 limma powers differential expression analyses for RNA-sequencing and microarray studies Nucleic acids research gkv007 PMC4402510 25605792
- Roberts EW Broz ML Binnewies M Headley MB Nelson AE Wolf DM Kaisho T Bogunovic D Bhardwaj N Krummel MF 2016 Critical Role for CD103(+)/CD141(+) Dendritic Cells Bearing CCR7 for Tumor Antigen Trafficking and Priming of T Cell Immunity in Melanoma Cancer Cell 30 324 336 27424807 PMC5374862
- Robins H Desmarais C Matthis J Livingston R Andriesen J Reijonen H Carlson C Nepom G Yee C Cerosaletti K 2012 Ultra-sensitive detection of rare T cell clones Journal of immunological methods 375 14 19 21945395 PMC3721519
- Robins HS Campregher PV Srivastava SK Wacher A Turtle CJ Kahsai O Riddell SR Warren EH Carlson CS 2009 Comprehensive assessment of T-cell receptor beta-chain diversity in alphabeta T cells Blood 114 4099 4107 19706884 PMC2774550
- Robinson MD Oshlack A 2010 A scaling normalization method for differential expression analysis of RNA-seq data Genome Biol 11 R25 20196867 PMC2864565
- Salmon H Franciszkiewicz K Damotte D Dieu-Nosjean MC Validire P Trautmann A Mami-Chouaib F Donnadieu E 2012 Matrix architecture defines the preferential localization and migration of T cells into the stroma of human lung tumors J Clin Invest 122 899 910 22293174 PMC3287213
- Salmon H Idoyaga J Rahman A Leboeuf M Remark R Jordan S Casanova-Acebes M Khudoynazarova M Agudo J Tung N 2016 Expansion and Activation of CD103(+) Dendritic Cell Progenitors at the Tumor Site Enhances Tumor Responses to Therapeutic PD-L1 and BRAF Inhibition Immunity 44 924 938 27096321 PMC4980762
- Sánchez-Paulete AR Cueto FJ Martínez-López M Labiano S Morales-Kastresana A Rodríguez-Ruiz ME Jure-Kunkel M Azpilikueta A Aznar MA Quetglas JI 2016 Cancer Immunotherapy with Immunomodulatory Anti-CD137 and Anti–PD-1 Monoclonal Antibodies Requires BATF3-Dependent Dendritic Cells Cancer Discovery 6 71 79 26493961 PMC5036540
- Spira A Beane JE Shah V Steiling K Liu G Schembri F Gilman S Dumas YM Calner P Sebastiani P 2007 Airway epithelial gene expression in the diagnostic evaluation of smokers with suspect lung cancer Nat Med 13 361 366 17334370
- Suzuki K Kadota K Sima CS Nitadori J Rusch VW Travis WD Sadelain M Adusumilli PS 2013 Clinical impact of immune microenvironment in stage I lung adenocarcinoma: tumor interleukin-12 receptor beta2 (IL-12Rbeta2), IL-7R, and stromal FoxP3/CD3 ratio are independent predictors of recurrence J Clin Oncol 31 490 498 23269987 PMC3731922
- Turley SJ Cremasco V Astarita JL 2015 Immunological hallmarks of stromal cells in the tumour microenvironment Nat Rev Immunol 15 669 682 26471778
- van der Maaten L 2014 Accelerating t-SNE using tree-based algorithms Journal of machine learning research 15 3221 3245
- van der Maaten L Hinton G 2008 Visualizing Data using t-SNE Journal of Machine Learning Research 9 2579 2605
- Wendel M Galani IE Suri-Payer E Cerwenka A 2008 Natural killer cell accumulation in tumors is dependent on IFN-gamma and CXCR3 ligands Cancer Res 68 8437 8445 18922917
- Yona S Jung S 2010 Monocytes: subsets, origins, fates and functions Curr Opin Hematol 17 53 59 19770654
- Yoshie O Matsushima K 2015 CCR4 and its ligands: from bench to bedside Int Immunol 27 11 20 25087232
- Yu H Lee H Herrmann A Buettner R Jove R 2014 Revisiting STAT3 signalling in cancer: new and unexpected biological functions Nat Rev Cancer 14 736 746 25342631
- Yu YR Hotten DF Malakhau Y Volker E Ghio AJ Noble PW Kraft M Hollingsworth JW Gunn MD Tighe RM 2016 Flow Cytometric Analysis of Myeloid Cells in Human Blood, Bronchoalveolar Lavage, and Lung Tissues Am J Respir Cell Mol Biol 54 13 24 26267148 PMC4742930
- Zhu W Germain C Liu Z Sebastian Y Devi P Knockaert S Brohawn P Lehmann K Damotte D Validire P 2015 A high density of tertiary lymphoid structure B cells in lung tumors is associated with increased CD4+ T cell receptor repertoire clonality OncoImmunology 4 e1051922 26587322 PMC4635865
- Zhu YM Webster SJ Flower D Woll PJ 2004 Interleukin-8/CXCL8 is a growth factor for human lung cancer cells Br J Cancer 91 1970 1976 15545974 PMC2409768
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Binnewies, M., Roberts, E. W., Kersten, K., Chan, V., Fearon, D. F., Merad, M., Coussens, L. M., Gabrilovich, D. I., Ostrand-Rosenberg, S., Hedrick, C. C., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0014-x · Cited by 6,145 · see citing works
Self-citationThe evolving tumor microenvironment: From cancer initiation to metastatic outgrowth
de Visser, K. E., & Joyce, J. A. (2023) · Cancer Cell · doi:10.1016/j.ccell.2023.02.016 · Cited by 4,059 · see citing works
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Fridman, W. H., Zitvogel, L., Sautès–Fridman, C., & Kroemer, G. (2017) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2017.101 · Cited by 2,263 · see citing works
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Roles of the immune system in cancer: From tumor initiation to metastatic progression
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Böttcher, J. P., Bonavita, E., Chakravarty, P., Blees, H., Cabeza-Cabrerizo, M., Sammicheli, S., Rogers, N. C., Sahai, E., Zelenay, S., & Reis e Sousa, C. (2018) · Cell · doi:10.1016/j.cell.2018.01.004 · Cited by 1,857 · see citing works
Landscape and Dynamics of Single Immune Cells in Hepatocellular Carcinoma
Zhang, Q., He, Y., Luo, N., Patel, S. J., Han, Y., Gao, R., Modak, M., Carotta, S., Haslinger, C., Kind, D., et al. (2019) · Cell · doi:10.1016/j.cell.2019.10.003 · Cited by 1,624 · see citing works
Organoid modeling of the tumor immune microenvironment
Neal, J. T., Li, X., Zhu, J., Giangarra, V., Grzeskowiak, C. L., Ju, J., Liu, I. H., Chiou, S.-H., Salahudeen, A. A., Smith, A. R., et al. (2018) · Cell · doi:10.1016/j.cell.2018.11.021 · Cited by 1,556 · see citing works
Bystander CD8+ T cells are abundant and phenotypically distinct in human tumour infiltrates
Simoni, Y., Becht, E., Fehlings, M., Loh, C. Y., Koo, S.-L., Teng, K. W. W., Yeong, J. P. S., Nahar, R., Zhang, T., Kared, H., et al. (2018) · Nature · doi:10.1038/s41586-018-0130-2 · Cited by 1,370 · see citing works
Distinct cellular mechanisms underlie anti-CTLA-4 and anti-PD-1 checkpoint blockade
Wei, S. C., Levine, J. H., Cogdill, A. P., Zhao, Y., Anang, N.-A. A. S., Andrews, M. C., Sharma, P., Wang, J., Wargo, J. A., Pe’er, D., et al. (2017) · Cell · doi:10.1016/j.cell.2017.07.024 · Cited by 1,302 · see citing works
Self-citationLi, H., van der Leun, A. M., Yofe, I., Lubling, Y., Gelbard-Solodkin, D., van Akkooi, A. C. J., van den Braber, M., Rozeman, E. A., Haanen, J. B. A. G., Blank, C. U., et al. (2019) · Cell · doi:10.1016/j.cell.2018.11.043 · Cited by 1,101 · see citing works
Self-citationA natural killer–dendritic cell axis defines checkpoint therapy–responsive tumor microenvironments
Barry, K. C., Hsu, J., Broz, M. L., Cueto, F. J., Binnewies, M., Combes, A. J., Nelson, A. E., Loo, K., Kumar, R., Rosenblum, M. D., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0085-8 · Cited by 1,021 · see citing works
Single-cell immune landscape of human atherosclerotic plaques
Fernandez, D. M., Rahman, A. H., Fernandez, N. F., Chudnovskiy, A., Amir, E.-A. D., Amadori, L., Khan, N. S., Wong, C. K., Shamailova, R., Hill, C. A., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0590-4 · Cited by 970 · see citing works
Self-citationNatural killer cells in cancer biology and therapy
Wu, S.-Y., Fu, T., Jiang, Y.-Z., & Shao, Z.-M. (2020) · Molecular Cancer · doi:10.1186/s12943-020-01238-x · Cited by 863 · see citing works
Single-cell analysis reveals fibroblast clusters linked to immunotherapy resistance in cancer.
Kieffer, Y., Hocine, H. R., Gentric, G., Pelon, F., Bernard, C., Bourachot, B., Lameiras, S., Albergante, L., Bonneau, C., Guyard, A., et al. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-1384 · Cited by 910 · see citing works
Zhang, Y., Chen, H., Mo, H., Hu, X., Gao, R., Zhao, Y., Liu, B., Niu, L., Sun, X., Yu, X., et al. (2021) · Cancer Cell · doi:10.1016/j.ccell.2021.09.010 · Cited by 783 · see citing works
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Park, M. D., Silvin, A., Ginhoux, F., & Merad, M. (2022) · Cell · doi:10.1016/j.cell.2022.10.007 · Cited by 644 · see citing works
Self-citationTREM2 Modulation Remodels the Tumor Myeloid Landscape Enhancing Anti-PD-1 Immunotherapy
Molgora, M., Esaulova, E., Vermi, W., Hou, J., Chen, Y., Luo, J., Brioschi, S., Bugatti, M., Omodei, A. S., Ricci, B., et al. (2020) · Cell · doi:10.1016/j.cell.2020.07.013 · Cited by 656 · see citing works
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Böttcher, J. P., & Reis e Sousa, C. (2018) · Trends in Cancer · doi:10.1016/j.trecan.2018.09.001 · Cited by 607 · see citing works
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Blériot, C., Chakarov, S., & Ginhoux, F. (2020) · Immunity · doi:10.1016/j.immuni.2020.05.014 · Cited by 507 · see citing works
Andersson, A., Larsson, L., Stenbeck, L., Salmén, F., Ehinger, A., Wu, S. Z., Al-Eryani, G., Roden, D., Swarbrick, A., Borg, Å., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-26271-2 · Cited by 404 · see citing works
Magen, A., Hamon, P., Fiaschi, N., Soong, B. Y., Park, M. D., Mattiuz, R., Humblin, E., Troncoso, L., D’souza, D., Dawson, T., et al. (2023) · Nature Medicine · doi:10.1038/s41591-023-02345-0 · Cited by 429 · see citing works
Self-citationColonna, M. (2023) · Nature Reviews Immunology · doi:10.1038/s41577-023-00837-1 · Cited by 394 · see citing works
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Goswami, S., Walle, T., Cornish, A. E., Basu, S., Anandhan, S., Fernandez, I., Vence, L., Blando, J., Zhao, H., Yadav, S. S., et al. (2020) · Nature Medicine · doi:10.1038/s41591-019-0694-x · Cited by 356 · see citing works
Wei, S. C., Anang, N.-A. A. S., Sharma, R., Andrews, M. C., Reuben, A., Levine, J. H., Cogdill, A. P., Mancuso, J. J., Wargo, J. A., Pe’er, D., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1821218116 · Cited by 359 · see citing works
Self-citationHe, L., Jhong, J.-H., Chen, Q., Huang, K.-Y., Strittmatter, K., Kreuzer, J., DeRan, M., Wu, X., Lee, T.-Y., Slavov, N., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109955 · Cited by 354 · see citing works
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Chi, Y., Remsik, J., Kiseliovas, V., Derderian, C., Sener, U., Alghader, M., Saadeh, F., Nikishina, K., Bale, T., Iacobuzio-Donahue, C., et al. (2020) · Science · doi:10.1126/science.aaz2193 · Cited by 320 · see citing works
Self-citationLiu, Y., Zugazagoitia, J., Ahmed, F. S., Henick, B. S., Gettinger, S. N., Herbst, R. S., Schalper, K. A., & Rimm, D. L. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-1040 · Cited by 322 · see citing works
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Oetjen, K. A., Lindblad, K. E., Goswami, M., Gui, G., Dagur, P. K., Lai, C., Dillon, L. W., McCoy, J. P., & Hourigan, C. S. (2018) · JCI Insight · doi:10.1172/jci.insight.124928 · Cited by 272 · see citing works
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Rood, J. E., Maartens, A., Hupalowska, A., Teichmann, S. A., & Regev, A. (2022) · Nature Medicine · doi:10.1038/s41591-022-02104-7 · Cited by 222 · see citing works
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Reuben, A., Zhang, J., Chiou, S.-H., Gittelman, R. M., Li, J., Lee, W.-C., Fujimoto, J., Behrens, C., Liu, X., Wang, F., et al. (2020) · Nature Communications · doi:10.1038/s41467-019-14273-0 · Cited by 220 · see citing works
Self-citation3D-3-culture: a tool to unveil macrophage plasticity in the tumour microenvironment
Rebelo, S. P., Pinto, C., Martins, T. R., Harrer, N., Estrada, M. F., Loza-Alvarez, P., Cabeçadas, J., Alves, P. M., Gualda, E. J., Sommergruber, W., et al. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.02.030 · Cited by 227 · see citing works
Best, S. A., De Souza, D. P., Kersbergen, A., Policheni, A. N., Dayalan, S., Tull, D., Rathi, V., Gray, D. H., Ritchie, M. E., McConville, M. J., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.02.006 · Cited by 217 · see citing works
Song, G., Shi, Y., Zhang, M., Goswami, S., Afridi, S., Meng, L., Ma, J., Chen, Y., Lin, Y., Zhang, J., et al. (2020) · Cell Discovery · doi:10.1038/s41421-020-00214-5 · Cited by 175 · see citing works
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Song, Q., Hawkins, G. A., Wudel, L., Chou, P., Forbes, E., Pullikuth, A. K., Liu, L., Jin, G., Craddock, L., Topaloglu, U., et al. (2019) · Cancer Medicine · doi:10.1002/cam4.2113 · Cited by 168 · see citing works
Single-Cell Genomics: A Stepping Stone for Future Immunology Discoveries
Giladi, A., & Amit, I. (2018) · Cell · doi:10.1016/j.cell.2017.11.011 · Cited by 168 · see citing works
Self-citationMyeloid cell heterogeneity in cancer: not a single cell alike
Kiss, M., Van Gassen, S., Movahedi, K., Saeys, Y., & Laoui, D. (2018) · Cellular Immunology · doi:10.1016/j.cellimm.2018.02.008 · Cited by 159 · see citing works
TREM2 macrophages induced by human lipids drive inflammation in acne lesions
Do, T. H., Ma, F., Andrade, P. R., Teles, R., de Andrade Silva, B. J., Hu, C., Espinoza, A., Hsu, J.-E., Cho, C.-S., Kim, M., et al. (2022) · Science Immunology · doi:10.1126/sciimmunol.abo2787 · Cited by 139 · see citing works
Lee, J. J., Bernard, V., Semaan, A., Monberg, M. E., Huang, J., Stephens, B. M., Lin, D., Rajapakshe, K. I., Weston, B. R., Bhutani, M. S., et al. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-3925 · Cited by 128 · see citing works
Sánchez-Paulete, A. R., Mateus-Tique, J., Mollaoglu, G., Nielsen, S. R., Marks, A., Lakshmi, A., Khan, J. A., Wilk, C. M., Pia, L., Baccarini, A., et al. (2022) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-21-1075 · Cited by 98 · see citing works
The Multifaceted Roles of Macrophages in NAFLD Pathogenesis
Vonderlin, J., Chavakis, T., Sieweke, M., & Tacke, F. (2023) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2023.03.002 · Cited by 96 · see citing works
Wang, L., Sfakianos, J. P., Beaumont, K. G., Akturk, G., Horowitz, A., Sebra, R. P., Farkas, A. M., Gnjatic, S., Hake, A., Izadmehr, S., et al. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-4574 · Cited by 97 · see citing works
Self-citationUsing single‐cell multiple omics approaches to resolve tumor heterogeneity
Ortega, M. A., Poirion, O., Zhu, X., Huang, S., Wolfgruber, T. K., Sebra, R., & Garmire, L. X. (2017) · Clinical and Translational Medicine · doi:10.1186/s40169-017-0177-y · Cited by 81 · see citing works
Schalck, A., Sakellariou-Thompson, D., Forget, M.-A., Sei, E., Hughes, T. G., Reuben, A., Bai, S., Hu, M., Kumar, T., Hurd, M. W., et al. (2022) · Cancer Discovery · doi:10.1158/2159-8290.cd-21-1248 · Cited by 85 · see citing works
Automatic cell type identification methods for single-cell RNA sequencing
Xie, B., Jiang, Q., Mora, A., & Li, X. (2021) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2021.10.027 · Cited by 66 · see citing works
Uncovering axes of variation among single-cell cancer specimens
Chen, W. S., Zivanovic, N., van Dijk, D., Wolf, G., Bodenmiller, B., & Krishnaswamy, S. (2020) · Nature Methods · doi:10.1038/s41592-019-0689-z · Cited by 48 · see citing works
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Herring, C. A., Chen, B., McKinley, E. T., & Lau, K. S. (2018) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2018.01.023 · Cited by 35 · see citing works
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Marron, T. U., Galsky, M. D., Taouli, B., Fiel, M. I., Ward, S., Kim, E., Yankelevitz, D., Doroshow, D., Guttman-Yassky, E., Ungar, B., et al. (2022) · Nature Medicine · doi:10.1038/s41591-022-01681-x · Cited by 30 · see citing works
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Caronni, N., Montaldo, E., Mezzanzanica, L., Cilenti, F., Genua, M., & Ostuni, R. (2021) · Immunological Reviews · doi:10.1111/imr.12944 · Cited by 6 · see citing works
Immunosuppression and phenotypic plasticity in an atlas of human hepatocholangiocarcinoma
Li, Y., Xun, Z., Long, J., Sun, H., Yang, X., Wang, Y., Wang, Y., Xue, J., Zhang, N., Zhang, J., et al. (2024) · Hepatobiliary Surgery and Nutrition · doi:10.21037/hbsn-23-400 · Cited by 2 · see citing works
- Authors
- Lavin, Y., Kobayashi, S., Leader, A., Amir, E.-A. D., Elefant, N., Bigenwald, C., Remark, R., Sweeney, R., Becker, C. D., Levine, J. H., Meinhof, K., Chow, A., Kim-Shulze, S., Wolf, A., Medaglia, C., Li, H., Rytlewski, J. A., Emerson, R. O., Solovyov, A., Greenbaum, B. D., Sanders, C., Vignali, M., Beasley, M. B., Flores, R., Gnjatic, S., Pe’er, D., Rahman, A., Amit, I., & Merad, M.
- Affiliations
- Tisch Cancer Institute (US)
- Weizmann Institute of Science (IL)
- Icahn School of Medicine at Mount Sinai (US)
- Adaptive Biotechnologies (United States) (US)
- ORCID
- Lavin, Yonit
- Kobayashi, Soma
- Leader, Andrew
- Elefant, Naama
- Bigenwald, Camille
- Sweeney, Robert
- Chow, Andrew
- Wolf, Andrea
- Medaglia, Chiara
- Li, Hanjie
- Rytlewski, Julie A.
- Emerson, Ryan O.
- Solovyov, Alexander
- Greenbaum, Benjamin D.
- Sanders, Catherine
- Vignali, Marissa
- Beasley, Mary Beth
- Flores, Raja
- Gnjatic, Sacha
- Pe’er, Dana
- Rahman, Adeeb
- Amit, Ido
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2017-05
- Volume
- 169
- Issue
- 4
- Pages
- 750-765.e17
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC5737939
- OpenAlex
- W2611596972
- Cited by
- 1,209
- References
- 9
- Citations by year
- 2026: 78 · 2025: 99 · 2024: 99 · 2023: 116 · 2022: 175 · 2021: 193 · 2020: 175 · 2019: 120 · 2018: 108 · 2017: 41 · 2015: 1
- FWCI
- 53.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Foundation pour la Recherche Medicale (DEA20150633125)
- NIH (R01, R01 CA173861, U19AI128949, U24 AI 118644, U19 AI 117873-01)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- early-stage lung adenocarcinoma, tumor immune microenvironment, innate immunity, T cell compartment, natural killer cells, tumor-infiltrating myeloid cells, barcoding, stage I lung cancer
- MeSH terms
- Adenocarcinoma of Lung, Adenocarcinoma, Dendritic Cells, Humans, Immunity, Innate, Killer Cells, Natural, Lung Neoplasms, Macrophages, T-Lymphocytes, Single-Cell Analysis, Tumor Microenvironment
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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