{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T17:55:06Z","timestamp":1792086906883,"version":"4.4.0"},"reference-count":49,"publisher":"American Association for Cancer Research (AACR)","issue":"3","funder":[{"DOI":"10.13039\/501100000015","name":"Canadian Cancer Society Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000015","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004376","name":"Terry Fox Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004376","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008732","name":"Japanese Society for the Promotion of Science Uehara Memorial Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008732","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008880","name":"Kanae Foundation for the Promotion of Medical Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008880","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000245","name":"Michael Smith Foundation for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000245","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>Hodgkin lymphoma is characterized by an extensively dominant tumor microenvironment (TME) composed of different types of noncancerous immune cells with rare malignant cells. Characterization of the cellular components and their spatial relationship is crucial to understanding cross-talk and therapeutic targeting in the TME. We performed single-cell RNA sequencing of more than 127,000 cells from 22 Hodgkin lymphoma tissue specimens and 5 reactive lymph nodes, profiling for the first time the phenotype of the Hodgkin lymphoma\u2013specific immune microenvironment at single-cell resolution. Single-cell expression profiling identified a novel Hodgkin lymphoma\u2013associated subset of T cells with prominent expression of the inhibitory receptor LAG3, and functional analyses established this LAG3+ T-cell population as a mediator of immunosuppression. Multiplexed spatial assessment of immune cells in the microenvironment also revealed increased LAG3+ T cells in the direct vicinity of MHC class II\u2013deficient tumor cells. Our findings provide novel insights into TME biology and suggest new approaches to immune-checkpoint targeting in Hodgkin lymphoma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance:<\/jats:title>\n                    <jats:p>We provide detailed functional and spatial characteristics of immune cells in classic Hodgkin lymphoma at single-cell resolution. Specifically, we identified a regulatory T-cell\u2013like immunosuppressive subset of LAG3+ T cells contributing to the immune-escape phenotype. Our insights aid in the development of novel biomarkers and combination treatment strategies targeting immune checkpoints.<\/jats:p>\n                    <jats:p>See related commentary by Fisher and Oh, p. 342.<\/jats:p>\n                    <jats:p>This article is highlighted in the In This Issue feature, p. 327<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1158\/2159-8290.cd-19-0680","type":"journal-article","created":{"date-parts":[[2019,12,19]],"date-time":"2019-12-19T14:45:10Z","timestamp":1576766710000},"page":"406-421","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":226,"title":["Single-Cell Transcriptome Analysis Reveals Disease-Defining T-cell Subsets in the Tumor Microenvironment of Classic Hodgkin Lymphoma"],"prefix":"10.1158","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6782-8361","authenticated-orcid":false,"given":"Tomohiro","family":"Aoki","sequence":"first","affiliation":[{"name":"1Centre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada."},{"name":"2Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren C.","family":"Chong","sequence":"additional","affiliation":[{"name":"1Centre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuyoshi","family":"Takata","sequence":"additional","affiliation":[{"name":"1Centre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katy","family":"Milne","sequence":"additional","affiliation":[{"name":"3Deeley Research Centre, British Columbia Cancer, Vancouver, British Columbia, Canada."},{"name":"4Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monirath","family":"Hav","sequence":"additional","affiliation":[{"name":"5Cedars-Sinai Medical Center, Los Angeles, California."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Colombo","sequence":"additional","affiliation":[{"name":"5Cedars-Sinai Medical Center, Los Angeles, California."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A.","family":"Chavez","sequence":"additional","affiliation":[{"name":"1Centre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Nissen","sequence":"additional","affiliation":[{"name":"6Terry Fox Laboratory, British Columbia Cancer, Vancouver, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuehai","family":"Wang","sequence":"additional","affiliation":[{"name":"6Terry Fox Laboratory, British Columbia Cancer, Vancouver, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Miyata-Takata","sequence":"additional","affiliation":[{"name":"1Centre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivian","family":"Lam","sequence":"additional","affiliation":[{"name":"6Terry Fox Laboratory, British Columbia Cancer, Vancouver, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Vigan\u00f2","sequence":"additional","affiliation":[{"name":"1Centre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada."},{"name":"2Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce W.","family":"Woolcock","sequence":"additional","affiliation":[{"name":"1Centre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ad\u00e8le","family":"Telenius","sequence":"additional","affiliation":[{"name":"1Centre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael Y.","family":"Li","sequence":"additional","affiliation":[{"name":"1Centre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada."},{"name":"2Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon","family":"Healy","sequence":"additional","affiliation":[{"name":"1Centre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chanel","family":"Ghesquiere","sequence":"additional","affiliation":[{"name":"3Deeley Research Centre, British Columbia Cancer, Vancouver, British Columbia, Canada."},{"name":"4Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Kos","sequence":"additional","affiliation":[{"name":"3Deeley Research Centre, British Columbia Cancer, Vancouver, British Columbia, Canada."},{"name":"4Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Talia","family":"Goodyear","sequence":"additional","affiliation":[{"name":"3Deeley Research Centre, British Columbia Cancer, Vancouver, British Columbia, Canada."},{"name":"4Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Veldman","sequence":"additional","affiliation":[{"name":"7Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen W.","family":"Zhang","sequence":"additional","affiliation":[{"name":"8Department of Molecular Oncology, British Columbia Cancer, Vancouver, British Columbia, Canada."},{"name":"9Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jubin","family":"Kim","sequence":"additional","affiliation":[{"name":"6Terry Fox Laboratory, British Columbia Cancer, Vancouver, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saeed","family":"Saberi","sequence":"additional","affiliation":[{"name":"8Department of Molecular Oncology, British Columbia Cancer, Vancouver, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiarui","family":"Ding","sequence":"additional","affiliation":[{"name":"8Department of Molecular Oncology, British Columbia Cancer, Vancouver, British Columbia, Canada."},{"name":"10Broad Institute of MIT and Harvard, Cambridge, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Farinha","sequence":"additional","affiliation":[{"name":"1Centre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew P.","family":"Weng","sequence":"additional","affiliation":[{"name":"6Terry Fox Laboratory, British Columbia Cancer, Vancouver, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerry J.","family":"Savage","sequence":"additional","affiliation":[{"name":"1Centre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W.","family":"Scott","sequence":"additional","affiliation":[{"name":"1Centre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald","family":"Krystal","sequence":"additional","affiliation":[{"name":"6Terry Fox Laboratory, British Columbia Cancer, Vancouver, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4445-5539","authenticated-orcid":false,"given":"Brad H.","family":"Nelson","sequence":"additional","affiliation":[{"name":"3Deeley Research Centre, British Columbia Cancer, Vancouver, British Columbia, Canada."},{"name":"4Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada."},{"name":"11Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Mottok","sequence":"additional","affiliation":[{"name":"1Centre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada."},{"name":"12Institute of Human Genetics, Ulm University and Ulm University Medical Center, Ulm, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akil","family":"Merchant","sequence":"additional","affiliation":[{"name":"5Cedars-Sinai Medical Center, Los Angeles, California."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sohrab P.","family":"Shah","sequence":"additional","affiliation":[{"name":"2Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada."},{"name":"8Department of Molecular Oncology, British Columbia Cancer, Vancouver, British Columbia, Canada."},{"name":"9Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Steidl","sequence":"additional","affiliation":[{"name":"1Centre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada."},{"name":"2Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1086","published-online":{"date-parts":[[2020,3,3]]},"reference":[{"key":"2022060622202408800_bib1","volume-title":"WHO classification of tumours of haematopoietic and lymphoid tissues. Revised 4th ed","author":"Swerdlow","year":"2017"},{"key":"2022060622202408800_bib2","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.1182\/blood-2017-09-772632","article-title":"Biology of classical Hodgkin lymphoma: implications for prognosis and novel therapies","volume":"131","author":"Mottok","year":"2018","journal-title":"Blood"},{"key":"2022060622202408800_bib3","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1097\/PPO.0000000000000334","article-title":"Novel biomarker approaches in classic Hodgkin lymphoma","volume":"24","author":"Aoki","year":"2018","journal-title":"Cancer J"},{"key":"2022060622202408800_bib4","doi-asserted-by":"crossref","first-page":"3722","DOI":"10.1200\/JCO.2017.72.7925","article-title":"Prognostic model to predict post-autologous stem-cell transplantation outcomes in classical Hodgkin lymphoma","volume":"35","author":"Chan","year":"2017","journal-title":"J Clin Oncol"},{"key":"2022060622202408800_bib5","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/nature09754","article-title":"MHC class II transactivator CIITA is a recurrent gene fusion partner in lymphoid cancers","volume":"471","author":"Steidl","year":"2011","journal-title":"Nature"},{"key":"2022060622202408800_bib6","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1056\/NEJMoa0905680","article-title":"Tumor-associated macrophages and survival in classic Hodgkin's lymphoma","volume":"362","author":"Steidl","year":"2010","journal-title":"N Engl J Med"},{"key":"2022060622202408800_bib7","doi-asserted-by":"crossref","first-page":"2125","DOI":"10.1200\/JCO.2016.72.1316","article-title":"Phase II study of the efficacy and safety of pembrolizumab for relapsed\/refractory classic Hodgkin lymphoma","volume":"35","author":"Chen","year":"2017","journal-title":"J Clin Oncol"},{"key":"2022060622202408800_bib8","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1200\/JCO.2017.76.0793","article-title":"Nivolumab for relapsed\/refractory classic Hodgkin lymphoma after failure of autologous hematopoietic cell transplantation: extended follow-up of the multicohort single-arm phase II CheckMate 205 trial","volume":"36","author":"Armand","year":"2018","journal-title":"J Clin Oncol"},{"key":"2022060622202408800_bib9","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.1200\/JCO.2011.38.0410","article-title":"Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin's lymphoma","volume":"30","author":"Younes","year":"2012","journal-title":"J Clin Oncol"},{"key":"2022060622202408800_bib10","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1182\/blood-2018-04-843714","article-title":"Mass cytometry of Hodgkin lymphoma reveals a CD4(+) regulatory T-cell-rich and exhausted T-effector microenvironment","volume":"132","author":"Cader","year":"2018","journal-title":"Blood"},{"key":"2022060622202408800_bib11","doi-asserted-by":"crossref","first-page":"2856","DOI":"10.1182\/blood-2013-06-508044","article-title":"Defining characteristics of classical Hodgkin lymphoma microenvironment T-helper cells","volume":"122","author":"Greaves","year":"2013","journal-title":"Blood"},{"key":"2022060622202408800_bib12","first-page":"2059","article-title":"The microenvironmental niche in classic Hodgkin lymphoma is enriched for CTLA-4-positive T-cells that are PD-1-negative","volume":"134","author":"Patel","year":"2019","journal-title":"Blood"},{"key":"2022060622202408800_bib13","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1016\/j.cell.2018.05.060","article-title":"Single-cell map of diverse immune phenotypes in the breast tumor microenvironment","volume":"174","author":"Azizi","year":"2018","journal-title":"Cell"},{"key":"2022060622202408800_bib14","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1038\/nbt.2938","article-title":"Linking T-cell receptor sequence to functional phenotype at the single-cell level","volume":"32","author":"Han","year":"2014","journal-title":"Nat Biotechnol"},{"key":"2022060622202408800_bib15","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nprot.2016.154","article-title":"Single-cell barcoding and sequencing using droplet microfluidics","volume":"12","author":"Zilionis","year":"2017","journal-title":"Nat Protoc"},{"key":"2022060622202408800_bib16","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1016\/j.cell.2015.04.044","article-title":"Droplet barcoding for single-cell transcriptomics applied to embryonic stem cells","volume":"161","author":"Klein","year":"2015","journal-title":"Cell"},{"key":"2022060622202408800_bib17","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.cell.2011.01.004","article-title":"Densely interconnected transcriptional circuits control cell states in human hematopoiesis","volume":"144","author":"Novershtern","year":"2011","journal-title":"Cell"},{"key":"2022060622202408800_bib18","doi-asserted-by":"crossref","first-page":"16309","DOI":"10.1073\/pnas.0508237102","article-title":"IL-32 synergizes with nucleotide oligomerization domain (NOD) 1 and NOD2 ligands for IL-1beta and IL-6 production through a caspase 1-dependent mechanism","volume":"102","author":"Netea","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2022060622202408800_bib19","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1146\/annurev.pathol.4.110807.092209","article-title":"Pathogenesis of classical and lymphocyte-predominant Hodgkin lymphoma","volume":"4","author":"Schmitz","year":"2009","journal-title":"Annu Rev Pathol"},{"key":"2022060622202408800_bib20","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1111\/bjh.12980","article-title":"Epstein-Barr virus infection induces an increase of T regulatory type 1 cells in Hodgkin lymphoma patients","volume":"166","author":"Morales","year":"2014","journal-title":"Br J Haematol"},{"key":"2022060622202408800_bib21","doi-asserted-by":"crossref","first-page":"2280","DOI":"10.1182\/blood-2006-04-015164","article-title":"Expression of LAG-3 by tumor-infiltrating lymphocytes is coincident with the suppression of latent membrane antigen-specific CD8+ T-cell function in Hodgkin lymphoma patients","volume":"108","author":"Gandhi","year":"2006","journal-title":"Blood"},{"key":"2022060622202408800_bib22","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1038\/nm.3179","article-title":"Coexpression of CD49b and LAG-3 identifies human and mouse T regulatory type 1 cells","volume":"19","author":"Gagliani","year":"2013","journal-title":"Nat Med"},{"key":"2022060622202408800_bib23","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1111\/imr.12519","article-title":"LAG3 (CD223) as a cancer immunotherapy target","volume":"276","author":"Andrews","year":"2017","journal-title":"Immunol Rev"},{"key":"2022060622202408800_bib24","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1038\/nature13954","article-title":"PD-1 blockade induces responses by inhibiting adaptive immune resistance","volume":"515","author":"Tumeh","year":"2014","journal-title":"Nature"},{"key":"2022060622202408800_bib25","doi-asserted-by":"crossref","first-page":"2989","DOI":"10.1093\/bioinformatics\/btv325","article-title":"Diffusion maps for high-dimensional single-cell analysis of differentiation data","volume":"31","author":"Haghverdi","year":"2015","journal-title":"Bioinformatics"},{"key":"2022060622202408800_bib26","doi-asserted-by":"crossref","first-page":"7426","DOI":"10.1073\/pnas.0500334102","article-title":"Geometric diffusions as a tool for harmonic analysis and structure definition of data: diffusion maps","volume":"102","author":"Coifman","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2022060622202408800_bib27","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.immuni.2004.08.010","article-title":"Role of LAG-3 in regulatory T cells","volume":"21","author":"Huang","year":"2004","journal-title":"Immunity"},{"key":"2022060622202408800_bib28","doi-asserted-by":"crossref","first-page":"2237","DOI":"10.1002\/1521-4141(200208)32:8<2237::AID-IMMU2237>3.0.CO;2-2","article-title":"Growth and expansion of human T regulatory type 1 cells are independent from TCR activation but require exogenous cytokines","volume":"32","author":"Bacchetta","year":"2002","journal-title":"Eur J Immunol"},{"key":"2022060622202408800_bib29","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1038\/39614","article-title":"A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis","volume":"389","author":"Groux","year":"1997","journal-title":"Nature"},{"key":"2022060622202408800_bib30","doi-asserted-by":"crossref","first-page":"4283","DOI":"10.1182\/blood-2002-01-0099","article-title":"The role of cytokines in classical Hodgkin lymphoma","volume":"99","author":"Skinnider","year":"2002","journal-title":"Blood"},{"key":"2022060622202408800_bib31","doi-asserted-by":"crossref","first-page":"2687","DOI":"10.1016\/j.fertnstert.2008.01.109","article-title":"CXCL12 enhances exogenous CD4+CD25+ T cell migration and prevents embryo loss in non-obese diabetic mice","volume":"91","author":"Lin","year":"2009","journal-title":"Fertil Steril"},{"key":"2022060622202408800_bib32","doi-asserted-by":"crossref","first-page":"6439","DOI":"10.4049\/jimmunol.179.10.6439","article-title":"Preferential migration of T regulatory cells induced by IL-16","volume":"179","author":"McFadden","year":"2007","journal-title":"J Immunol"},{"key":"2022060622202408800_bib33","doi-asserted-by":"crossref","first-page":"3048","DOI":"10.1038\/onc.2016.458","article-title":"Cancer-FOXP3 directly activated CCL5 to recruit FOXP3(+)Treg cells in pancreatic ductal adenocarcinoma","volume":"36","author":"Wang","year":"2017","journal-title":"Oncogene"},{"key":"2022060622202408800_bib34","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1182\/blood-2016-04-711275","article-title":"TNF-alpha priming enhances CD4+FoxP3+ regulatory T-cell suppressive function in murine GVHD prevention and treatment","volume":"128","author":"Pierini","year":"2016","journal-title":"Blood"},{"key":"2022060622202408800_bib35","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1093\/jmcb\/mjr033","article-title":"TGF-beta: the sword, the wand, and the shield of FOXP3(+) regulatory T cells","volume":"4","author":"Tran","year":"2012","journal-title":"J Mol Cell Biol"},{"key":"2022060622202408800_bib36","doi-asserted-by":"crossref","first-page":"2000","DOI":"10.1158\/0008-5472.CAN-08-2360","article-title":"Regulatory T cells recruited through CCL22\/CCR4 are selectively activated in lymphoid infiltrates surrounding primary breast tumors and lead to an adverse clinical outcome","volume":"69","author":"Gobert","year":"2009","journal-title":"Cancer Res"},{"key":"2022060622202408800_bib37","doi-asserted-by":"crossref","first-page":"2286","DOI":"10.1002\/ijc.23392","article-title":"CCL17 and CCL22 chemokines within tumor microenvironment are related to accumulation of Foxp3+ regulatory T cells in gastric cancer","volume":"122","author":"Mizukami","year":"2008","journal-title":"Int J Cancer"},{"key":"2022060622202408800_bib38","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.jaut.2012.07.009","article-title":"Interleukin-6 induces the generation of IL-10-producing Tr1 cells and suppresses autoimmune tissue inflammation","volume":"40","author":"Jin","year":"2013","journal-title":"J Autoimmun"},{"key":"2022060622202408800_bib39","doi-asserted-by":"crossref","first-page":"3530","DOI":"10.1182\/blood-2012-06-439570","article-title":"Gene expression profiling of microdissected Hodgkin Reed-Sternberg cells correlates with treatment outcome in classical Hodgkin lymphoma","volume":"120","author":"Steidl","year":"2012","journal-title":"Blood"},{"key":"2022060622202408800_bib40","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1002\/eji.1830260533","article-title":"T cell major histocompatibility complex class II molecules down-regulate CD4+ T cell clone responses following LAG-3 binding","volume":"26","author":"Huard","year":"1996","journal-title":"Eur J Immunol"},{"key":"2022060622202408800_bib41","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1084\/jem.176.2.327","article-title":"Characterization of the lymphocyte activation gene 3-encoded protein. A new ligand for human leukocyte antigen class II antigens","volume":"176","author":"Baixeras","year":"1992","journal-title":"J Exp Med"},{"key":"2022060622202408800_bib42","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1182\/bloodadvances.2017007260","article-title":"Th17 immune microenvironment in Epstein-Barr virus-negative Hodgkin lymphoma: implications for immunotherapy","volume":"1","author":"Duffield","year":"2017","journal-title":"Blood Adv"},{"key":"2022060622202408800_bib43","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1200\/JCO.2017.77.3994","article-title":"Major histocompatibility complex class II and programmed death ligand 1 expression predict outcome after programmed death 1 blockade in classic Hodgkin lymphoma","volume":"36","author":"Roemer","year":"2018","journal-title":"J Clin Oncol"},{"key":"2022060622202408800_bib44","doi-asserted-by":"crossref","first-page":"8490","DOI":"10.1073\/pnas.1608873113","article-title":"Nonoverlapping roles of PD-1 and FoxP3 in maintaining immune tolerance in a novel autoimmune pancreatitis mouse model","volume":"113","author":"Zhang","year":"2016","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2022060622202408800_bib45","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.cell.2018.11.010","article-title":"Fibrinogen-like protein 1 is a major immune inhibitory ligand of LAG-3","volume":"176","author":"Wang","year":"2019","journal-title":"Cell"},{"key":"2022060622202408800_bib46","doi-asserted-by":"crossref","first-page":"3418","DOI":"10.1158\/0008-5472.CAN-13-2690","article-title":"LSECtin expressed on melanoma cells promotes tumor progression by inhibiting antitumor T-cell responses","volume":"74","author":"Xu","year":"2014","journal-title":"Cancer Res"},{"key":"2022060622202408800_bib47","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/s13059-016-0947-7","article-title":"Pooling across cells to normalize single-cell RNA sequencing data with many zero counts","volume":"17","author":"Lun","year":"2016","journal-title":"Genome Biol"},{"key":"2022060622202408800_bib48","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.cell.2015.05.047","article-title":"Data-driven phenotypic dissection of AML reveals progenitor-like cells that correlate with prognosis","volume":"162","author":"Levine","year":"2015","journal-title":"Cell"},{"key":"2022060622202408800_bib49","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1002\/path.5049","article-title":"Ruthenium counterstaining for imaging mass cytometry","volume":"244","author":"Catena","year":"2018","journal-title":"J Pathol"}],"container-title":["Cancer Discovery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/aacrjournals.org\/cancerdiscovery\/article-pdf\/10\/3\/406\/1813110\/406.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerdiscovery\/article-pdf\/10\/3\/406\/1813110\/406.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,6]],"date-time":"2022-06-06T18:20:59Z","timestamp":1654539659000},"score":1,"resource":{"primary":{"URL":"https:\/\/aacrjournals.org\/cancerdiscovery\/article\/10\/3\/406\/2507\/Single-Cell-Transcriptome-Analysis-Reveals-Disease"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,1]]},"references-count":49,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,3,3]]},"published-print":{"date-parts":[[2020,3,1]]}},"URL":"https:\/\/doi.org\/10.1158\/2159-8290.cd-19-0680","relation":{"has-preprint":[{"id-type":"doi","id":"10.1158\/2159-8290.22535404","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.22535404.v1","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.22535401.v1","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.c.6547852.v1","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.c.6547852","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.22535401","asserted-by":"object"}]},"ISSN":["2159-8274","2159-8290"],"issn-type":[{"value":"2159-8274","type":"print"},{"value":"2159-8290","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,1]]}}}