Journal Article
. 2016 Nov; 45(5):1135-1147.
doi: 10.1016/j.immuni.2016.10.021.

Transcriptional Landscape of Human Tissue Lymphocytes Unveils Uniqueness of Tumor-Infiltrating T Regulatory Cells

Marco De Simone 1 Alberto Arrigoni 1 Grazisa Rossetti 1 Paola Gruarin 1 Valeria Ranzani 1 Claudia Politano 1 Raoul J P Bonnal 1 Elena Provasi 1 Maria Lucia Sarnicola 1 Ilaria Panzeri 1 Monica Moro 1 Mariacristina Crosti 1 Saveria Mazzara 1 Valentina Vaira 2 Silvano Bosari 3 Alessandro Palleschi 4 Luigi Santambrogio 5 Giorgio Bovo 6 Nicola Zucchini 6 Mauro Totis 7 Luca Gianotti 8 Giancarlo Cesana 9 Roberto A Perego 9 Nirvana Maroni 10 Andrea Pisani Ceretti 10 Enrico Opocher 11 Raffaele De Francesco 1 Jens Geginat 1 Hendrik G Stunnenberg 12 Sergio Abrignani 13 Massimiliano Pagani 14 
Affiliations
  • PMID: 27851914
  •     56 References
  •     219 citations

Abstract

Tumor-infiltrating regulatory T lymphocytes (Treg) can suppress effector T cells specific for tumor antigens. Deeper molecular definitions of tumor-infiltrating-lymphocytes could thus offer therapeutic opportunities. Transcriptomes of T helper 1 (Th1), Th17, and Treg cells infiltrating colorectal or non-small-cell lung cancers were compared to transcriptomes of the same subsets from normal tissues and validated at the single-cell level. We found that tumor-infiltrating Treg cells were highly suppressive, upregulated several immune-checkpoints, and expressed on the cell surfaces specific signature molecules such as interleukin-1 receptor 2 (IL1R2), programmed death (PD)-1 Ligand1, PD-1 Ligand2, and CCR8 chemokine, which were not previously described on Treg cells. Remarkably, high expression in whole-tumor samples of Treg cell signature genes, such as LAYN, MAGEH1, or CCR8, correlated with poor prognosis. Our findings provide insights into the molecular identity and functions of human tumor-infiltrating Treg cells and define potential targets for tumor immunotherapy.

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Targeting ST2 expressing activated regulatory T cells in Kras-mutant lung cancer.
Byung-Seok Kim, Jelita Clinton, Qing Wang, Seon Hee Chang.
Oncoimmunology, 2020 Feb 01; 9(1). PMID: 32002289    Free PMC article.
Understanding the glioblastoma immune microenvironment as basis for the development of new immunotherapeutic strategies.
Ana Rita Pombo Antunes, Isabelle Scheyltjens, +3 authors, Jo A Van Ginderachter.
Elife, 2020 Feb 06; 9. PMID: 32014107    Free PMC article.
Review.
Cancer immunosurveillance by CD8 T cells.
José C Crispin, George C Tsokos.
F1000Res, 2020 Feb 25; 9. PMID: 32089832    Free PMC article.
Review.
Arrested Developments: CDK4/6 Inhibitor Resistance and Alterations in the Tumor Immune Microenvironment.
Jessica L F Teh, Andrew E Aplin.
Clin Cancer Res, 2018 Oct 06; 25(3). PMID: 30287548    Free PMC article.
Review.
A novel signature derived from immunoregulatory and hypoxia genes predicts prognosis in liver and five other cancers.
Wai Hoong Chang, Donall Forde, Alvina G Lai.
J Transl Med, 2019 Jan 11; 17(1). PMID: 30626396    Free PMC article.
Correlate tumor mutation burden with immune signatures in human cancers.
Xiaosheng Wang, Mengyuan Li.
BMC Immunol, 2019 Jan 13; 20(1). PMID: 30634925    Free PMC article.
Highly Cited.
Tumor-infiltrating human CD4+ regulatory T cells display a distinct TCR repertoire and exhibit tumor and neoantigen reactivity.
Mojgan Ahmadzadeh, Anna Pasetto, +4 authors, Steven A Rosenberg.
Sci Immunol, 2019 Jan 13; 4(31). PMID: 30635355    Free PMC article.
Highly Cited.
IL-27 confers a protumorigenic activity of regulatory T cells via CD39.
Young-Jun Park, Heeju Ryu, +4 authors, Yeonseok Chung.
Proc Natl Acad Sci U S A, 2019 Feb 06; 116(8). PMID: 30718407    Free PMC article.
Single-Cell Transcriptomics of Regulatory T Cells Reveals Trajectories of Tissue Adaptation.
Ricardo J Miragaia, Tomás Gomes, +13 authors, Sarah A Teichmann.
Immunity, 2019 Feb 10; 50(2). PMID: 30737144    Free PMC article.
Highly Cited.
LAYN Is a Prognostic Biomarker and Correlated With Immune Infiltrates in Gastric and Colon Cancers.
Jing-Hua Pan, Hong Zhou, +6 authors, Lijun Rong.
Front Immunol, 2019 Feb 15; 10. PMID: 30761122    Free PMC article.
Highly Cited.
Treg programming and therapeutic reprogramming in cancer.
Mariela A Moreno Ayala, Zehui Li, Michel DuPage.
Immunology, 2019 Mar 14; 157(3). PMID: 30866047    Free PMC article.
Review.
Guidance factors orchestrating regulatory T cell positioning in tissues during development, homeostasis, and response.
Thorsten R Mempel, Francesco Marangoni.
Immunol Rev, 2019 Apr 13; 289(1). PMID: 30977195    Free PMC article.
Review.
Regulation of regulatory T cells in cancer.
Julie Stockis, Rahul Roychoudhuri, Timotheus Y F Halim.
Immunology, 2019 Apr 30; 157(3). PMID: 31032905    Free PMC article.
Review.
Dysregulation of EMT Drives the Progression to Clinically Aggressive Sarcomatoid Bladder Cancer.
Charles C Guo, Tadeusz Majewski, +22 authors, Bogdan Czerniak.
Cell Rep, 2019 May 09; 27(6). PMID: 31067463    Free PMC article.
Identification of three subtypes of triple-negative breast cancer with potential therapeutic implications.
Pascal Jézéquel, Olivier Kerdraon, +11 authors, Mario Campone.
Breast Cancer Res, 2019 May 19; 21(1). PMID: 31101122    Free PMC article.
Estimation of immune cell content in tumor using single-cell RNA-seq reference data.
Xiaoqing Yu, Y Ann Chen, +2 authors, Xuefeng Wang.
BMC Cancer, 2019 Jul 22; 19(1). PMID: 31324168    Free PMC article.
Regulatory T Cells in Tumor Microenvironment and Approach for Anticancer Immunotherapy.
Jung-Ho Kim, Beom Seok Kim, Sang-Kyou Lee.
Immune Netw, 2020 Mar 12; 20(1). PMID: 32158592    Free PMC article.
Review.
The role of FOXP3+ regulatory T cells in human autoimmune and inflammatory diseases.
A Mohr, M Atif, +2 authors, M Miyara.
Clin Exp Immunol, 2019 Mar 05; 197(1). PMID: 30830965    Free PMC article.
Review.
Mechanisms of human FoxP3+ Treg cell development and function in health and disease.
M Attias, T Al-Aubodah, C A Piccirillo.
Clin Exp Immunol, 2019 Mar 14; 197(1). PMID: 30864147    Free PMC article.
Review.
Relationships Between Immune Landscapes, Genetic Subtypes and Responses to Immunotherapy in Colorectal Cancer.
Emilie Picard, Chris P Verschoor, Grace W Ma, Graham Pawelec.
Front Immunol, 2020 Mar 27; 11. PMID: 32210966    Free PMC article.
Review.
Depleting tumor-associated Tregs via nanoparticle-mediated hyperthermia to enhance anti-CTLA-4 immunotherapy.
Hongwei Chen, Xin Luan, +7 authors, Duxin Sun.
Nanomedicine (Lond), 2019 Dec 24; 15(1). PMID: 31868112    Free PMC article.
Preferential Infiltration of Unique Vγ9Jγ2-Vδ2 T Cells Into Glioblastoma Multiforme.
Mijeong Lee, Chanho Park, +8 authors, Tae Jin Kim.
Front Immunol, 2019 Apr 11; 10. PMID: 30967876    Free PMC article.
Tumour grade significantly correlates with total dysfunction of tumour tissue-infiltrating lymphocytes in renal cell carcinoma.
Atsunari Kawashima, Takayuki Kanazawa, +19 authors, Norio Nonomura.
Sci Rep, 2020 Apr 12; 10(1). PMID: 32277125    Free PMC article.
Interleukin-1 and Related Cytokines in the Regulation of Inflammation and Immunity.
Alberto Mantovani, Charles A Dinarello, Martina Molgora, Cecilia Garlanda.
Immunity, 2019 Apr 18; 50(4). PMID: 30995499    Free PMC article.
Highly Cited. Review.
The application and prospect of CDK4/6 inhibitors in malignant solid tumors.
Qi Du, Xiang Guo, +3 authors, Qin Li.
J Hematol Oncol, 2020 May 03; 13(1). PMID: 32357912    Free PMC article.
Review.
Targeting T cell activation in immuno-oncology.
S D Saibil, P S Ohashi.
Curr Oncol, 2020 May 06; 27(Suppl 2). PMID: 32368179    Free PMC article.
Review.
The liver as an immunological barrier redefined by single-cell analysis.
Zania Stamataki, Leo Swadling.
Immunology, 2020 Mar 17; 160(2). PMID: 32176810    Free PMC article.
Review.
Inducers, Attractors and Modulators of CD4+ Treg Cells in Non-Small-Cell Lung Cancer.
Mengxiao Xie, Jia Wei, Jian Xu.
Front Immunol, 2020 May 20; 11. PMID: 32425930    Free PMC article.
Review.
Recirculation and Residency of T Cells and Tregs: Lessons Learnt in Anacapri.
Silvia Piconese, Silvia Campello, Ambra Natalini.
Front Immunol, 2020 May 21; 11. PMID: 32431695    Free PMC article.
Review.
IRF4 instructs effector Treg differentiation and immune suppression in human cancer.
Giorgia Alvisi, Jolanda Brummelman, +18 authors, Enrico Lugli.
J Clin Invest, 2020 Mar 04; 130(6). PMID: 32125291    Free PMC article.
Bcl6 Preserves the Suppressive Function of Regulatory T Cells During Tumorigenesis.
Yiding Li, Zhiming Wang, +16 authors, Lifan Xu.
Front Immunol, 2020 Jun 02; 11. PMID: 32477338    Free PMC article.
A conserved intratumoral regulatory T cell signature identifies 4-1BB as a pan-cancer target.
Zachary T Freeman, Thomas R Nirschl, +17 authors, Charles G Drake.
J Clin Invest, 2020 Feb 06; 130(3). PMID: 32015231    Free PMC article.
T1D progression is associated with loss of CD3+CD56+ regulatory T cells that control CD8+ T cell effector functions.
Giuseppe Terrazzano, Sara Bruzzaniti, +20 authors, Mario Galgani.
Nat Metab, 2020 Jun 06; 2(2). PMID: 32500117    Free PMC article.
Assessment of Luminal and Basal Phenotypes in Bladder Cancer.
Charles C Guo, Jolanta Bondaruk, +18 authors, Bogdan Czerniak.
Sci Rep, 2020 Jun 18; 10(1). PMID: 32546765    Free PMC article.
Regulatory T cells specifically suppress conventional CD8αβ T cells in intestinal tumors of APCMin/+ mice.
Louis Szeponik, Paulina Akeus, +2 authors, Marianne Quiding-Järbrink.
Cancer Immunol Immunother, 2020 Mar 19; 69(7). PMID: 32185408    Free PMC article.
Unravelling the heterogeneity and dynamic relationships of tumor-infiltrating T cells by single-cell RNA sequencing analysis.
Xin Yu, Lei Zhang, +2 authors, Wenjun Ouyang.
J Leukoc Biol, 2020 Apr 10; 107(6). PMID: 32272497    Free PMC article.
Review.
Intratumoral CD4+ T Cells Mediate Anti-tumor Cytotoxicity in Human Bladder Cancer.
David Y Oh, Serena S Kwek, +17 authors, Lawrence Fong.
Cell, 2020 Jun 05; 181(7). PMID: 32497499    Free PMC article.
Tumor infiltrating T cells influence prognosis in stage I-III non-small cell lung cancer.
Arik Bernard Schulze, Georg Evers, +6 authors, Birthe Heitkötter.
J Thorac Dis, 2020 Jul 10; 12(5). PMID: 32642087    Free PMC article.
Two gene set variation indexes as potential diagnostic tool for sepsis.
Junyu Lu, Qian Li, +6 authors, Jianfeng Zhang.
Am J Transl Res, 2020 Jul 14; 12(6). PMID: 32655806    Free PMC article.
CD70 expression determines the therapeutic efficacy of expanded human regulatory T cells.
Rebeca Arroyo Hornero, Christos Georgiadis, +8 authors, Joanna Hester.
Commun Biol, 2020 Jul 16; 3(1). PMID: 32665635    Free PMC article.
Circulating immune cell phenotype dynamics reflect the strength of tumor-immune cell interactions in patients during immunotherapy.
Jason I Griffiths, Pierre Wallet, +13 authors, Andrea H Bild.
Proc Natl Acad Sci U S A, 2020 Jun 24; 117(27). PMID: 32571915    Free PMC article.
Analyzing and validating the prognostic value and mechanism of colon cancer immune microenvironment.
Xinyi Wang, Jinzhong Duanmu, +2 authors, Qunguang Jiang.
J Transl Med, 2020 Aug 30; 18(1). PMID: 32859214    Free PMC article.
Tumor-infiltrating CD62L+PD-1-CD8 T cells retain proliferative potential via Bcl6 expression and replenish effector T cells within the tumor.
Yu Gong, Toshihiro Suzuki, +2 authors, Naoko Nakano.
PLoS One, 2020 Aug 28; 15(8). PMID: 32845913    Free PMC article.
Clinical and prognostic significance of CC chemokine receptor type 8 protein expression in gastrointestinal stromal tumors.
Huai-Liang Li, Lin-Hua Wang, +6 authors, Wan-Jiang Xue.
World J Gastroenterol, 2020 Sep 05; 26(31). PMID: 32884223    Free PMC article.
Layilin augments integrin activation to promote antitumor immunity.
Kelly M Mahuron, Joshua M Moreau, +18 authors, Michael D Rosenblum.
J Exp Med, 2020 Jun 17; 217(9). PMID: 32539073    Free PMC article.
Turning the Tide Against Regulatory T Cells.
SeongJun Han, Aras Toker, Zhe Qi Liu, Pamela S Ohashi.
Front Oncol, 2019 May 07; 9. PMID: 31058083    Free PMC article.
Review.
TP53 Mutations Promote Immunogenic Activity in Breast Cancer.
Zhixian Liu, Zehang Jiang, +3 authors, Xiaosheng Wang.
J Oncol, 2019 Jul 06; 2019. PMID: 31275382    Free PMC article.
Correlate the TP53 Mutation and the HRAS Mutation with Immune Signatures in Head and Neck Squamous Cell Cancer.
Haoyu Lyu, Mengyuan Li, +2 authors, Xiaosheng Wang.
Comput Struct Biotechnol J, 2019 Aug 21; 17. PMID: 31428295    Free PMC article.
Human Tregs at the materno-fetal interface show site-specific adaptation reminiscent of tumor Tregs.
Judith Wienke, Laura Brouwers, +5 authors, Femke van Wijk.
JCI Insight, 2020 Aug 19; 5(18). PMID: 32809975    Free PMC article.
Immunomodulation by anticancer cell cycle inhibitors.
Giulia Petroni, Silvia C Formenti, Selina Chen-Kiang, Lorenzo Galluzzi.
Nat Rev Immunol, 2020 Apr 30; 20(11). PMID: 32346095    Free PMC article.
Review.
Ovarian Cancer Cells Promote Glycolysis Metabolism and TLR8-Mediated Metabolic Control of Human CD4+ T Cells.
Wenwen Shang, Rui Xu, +3 authors, Fang Wang.
Front Oncol, 2020 Oct 27; 10. PMID: 33102225    Free PMC article.
Intrahepatic TH17/TReg Cells in Homeostasis and Disease-It's All About the Balance.
Hannah K Drescher, Lea M Bartsch, Sabine Weiskirchen, Ralf Weiskirchen.
Front Pharmacol, 2020 Oct 31; 11. PMID: 33123017    Free PMC article.
Review.
Comprehensive analysis of prognostic immune-related genes associated with the tumor microenvironment of pancreatic ductal adenocarcinoma.
Shibai Yan, Juntao Fang, +2 authors, Feng Fang.
Oncol Lett, 2020 Nov 03; 20(6). PMID: 33133266    Free PMC article.
Transcriptional Control of Regulatory T Cells in Cancer: Toward Therapeutic Targeting?
Pierre Stéphan, Raphaëlle Lautraite, Allison Voisin, Yenkel Grinberg-Bleyer.
Cancers (Basel), 2020 Nov 05; 12(11). PMID: 33143070    Free PMC article.
Review.
CD39+ regulatory T cells accumulate in colon adenocarcinomas and display markers of increased suppressive function.
Filip Ahlmanner, Patrik Sundström, +6 authors, Marianne Quiding-Järbrink.
Oncotarget, 2019 Jan 18; 9(97). PMID: 30651930    Free PMC article.
Tumors establish resistance to immunotherapy by regulating Treg recruitment via CCR4.
Lisa A Marshall, Sachie Marubayashi, +16 authors, Oezcan Talay.
J Immunother Cancer, 2020 Nov 28; 8(2). PMID: 33243932    Free PMC article.
Immune suppressive landscape in the human esophageal squamous cell carcinoma microenvironment.
Yingxia Zheng, Zheyi Chen, +16 authors, Lisong Shen.
Nat Commun, 2020 Dec 10; 11(1). PMID: 33293583    Free PMC article.
Lung Cancer Survival in Patients With Autoimmune Disease.
Saya Jacob, Kian Rahbari, +8 authors, Victoria Villaflor.
JAMA Netw Open, 2020 Dec 15; 3(12). PMID: 33315114    Free PMC article.
Applications of Single-Cell Omics to Dissect Tumor Microenvironment.
Tingting Guo, Weimin Li, Xuyu Cai.
Front Genet, 2020 Dec 18; 11. PMID: 33329692    Free PMC article.
Review.
Human Tissue-Resident Memory T Cells in the Maternal-Fetal Interface. Lost Soldiers or Special Forces?
Caitlin S DeJong, Nicholas J Maurice, Stephen A McCartney, Martin Prlic.
Cells, 2020 Dec 20; 9(12). PMID: 33339211    Free PMC article.
Review.
Recirculating IL-1R2+ Tregs fine-tune intrathymic Treg development under inflammatory conditions.
Eirini Nikolouli, Yassin Elfaki, +7 authors, Jochen Huehn.
Cell Mol Immunol, 2020 Jan 29; 18(1). PMID: 31988493    Free PMC article.
Alternative Pathways of IL-1 Activation, and Its Role in Health and Disease.
Katerina Pyrillou, Laura C Burzynski, Murray C H Clarke.
Front Immunol, 2021 Jan 05; 11. PMID: 33391283    Free PMC article.
Review.
Interleukin-38 ameliorates poly(I:C) induced lung inflammation: therapeutic implications in respiratory viral infections.
Xun Gao, Paul Kay Sheung Chan, +7 authors, Chun-Kwok Wong.
Cell Death Dis, 2021 Jan 09; 12(1). PMID: 33414457    Free PMC article.
TISCH: a comprehensive web resource enabling interactive single-cell transcriptome visualization of tumor microenvironment.
Dongqing Sun, Jin Wang, +13 authors, Chenfei Wang.
Nucleic Acids Res, 2020 Nov 13; 49(D1). PMID: 33179754    Free PMC article.
Tissue-Resident Lymphocytes: Implications in Immunotherapy for Hepatocellular Carcinoma.
Ji Won Han, Seung Kew Yoon.
Int J Mol Sci, 2021 Jan 01; 22(1). PMID: 33379384    Free PMC article.
Review.
Mechanisms of Immunosuppression in Colorectal Cancer.
Yang Zhang, Ashwani Rajput, Ning Jin, Jing Wang.
Cancers (Basel), 2021 Jan 10; 12(12). PMID: 33419310    Free PMC article.
Review.
Oleic acid restores suppressive defects in tissue-resident FOXP3 Tregs from patients with multiple sclerosis.
Saige L Pompura, Allon Wagner, +4 authors, David A Hafler.
J Clin Invest, 2020 Nov 11; 131(2). PMID: 33170805    Free PMC article.
Wilms' Tumor Primary Cells Display Potent Immunoregulatory Properties on NK Cells and Macrophages.
Piera Filomena Fiore, Paola Vacca, +8 authors, Bruno Azzarone.
Cancers (Basel), 2021 Jan 14; 13(2). PMID: 33435455    Free PMC article.
IFN-γ and CD38 in Hyperprogressive Cancer Development.
Stefania Angelicola, Francesca Ruzzi, +6 authors, Arianna Palladini.
Cancers (Basel), 2021 Jan 21; 13(2). PMID: 33467713    Free PMC article.
Review.
Mapping the immune environment in clear cell renal carcinoma by single-cell genomics.
Nicholas Borcherding, Ajaykumar Vishwakarma, +7 authors, Weizhou Zhang.
Commun Biol, 2021 Jan 29; 4(1). PMID: 33504936    Free PMC article.
Regulation of Treg Functions by the Ubiquitin Pathway.
Elena Montauti, Deyu Fang.
Adv Exp Med Biol, 2021 Feb 02; 1278. PMID: 33523442
Intestinal Regulatory T Cells.
Vanessa R Figliuolo da Paz, Deepa R Jamwal, Pawel R Kiela.
Adv Exp Med Biol, 2021 Feb 02; 1278. PMID: 33523448
Understanding and Targeting Human Cancer Regulatory T Cells to Improve Therapy.
H Ryan Kolb, Nicholas Borcherding, Weizhou Zhang.
Adv Exp Med Biol, 2021 Feb 02; 1278. PMID: 33523451
The Therapeutic Potential of Regulatory T Cells: Challenges and Opportunities.
Fatemeh Bayati, Mahsa Mohammadi, +3 authors, Ehsan Sharif-Paghaleh.
Front Immunol, 2021 Feb 02; 11. PMID: 33519807    Free PMC article.
Review.
Tumour heterogeneity and intercellular networks of nasopharyngeal carcinoma at single cell resolution.
Yang Liu, Shuai He, +18 authors, Jin-Xin Bei.
Nat Commun, 2021 Feb 04; 12(1). PMID: 33531485    Free PMC article.
KRAS mutations are negatively correlated with immunity in colon cancer.
Xiaorui Fu, Xinyi Wang, +2 authors, Qunguang Jiang.
Aging (Albany NY), 2020 Dec 01; 13(1). PMID: 33254149    Free PMC article.
Evaluation of glucocorticoid-induced TNF receptor (GITR) expression in breast cancer and across multiple tumor types.
Mayanne M T Zhu, Samantha Burugu, +5 authors, Torsten O Nielsen.
Mod Pathol, 2020 May 01; 33(9). PMID: 32350416
The Adhesome Network: Key Components Shaping the Tumour Stroma.
Pinelopi A Nikolopoulou, Maria A Koufaki, Vassiliki Kostourou.
Cancers (Basel), 2021 Feb 13; 13(3). PMID: 33573141    Free PMC article.
Review.
Modulation of regulatory T cell function and stability by co-inhibitory receptors.
Liliana E Lucca, Margarita Dominguez-Villar.
Nat Rev Immunol, 2020 Apr 10; 20(11). PMID: 32269380
Review.
Single-Cell Analysis Reveals Characterization of Infiltrating T Cells in Moderately Differentiated Colorectal Cancer.
Xi Yang, Quan Qi, +6 authors, Shuwen Han.
Front Immunol, 2021 Feb 16; 11. PMID: 33584715    Free PMC article.
Interleukin-1 as Innate Mediator of T Cell Immunity.
Bram Van Den Eeckhout, Jan Tavernier, Sarah Gerlo.
Front Immunol, 2021 Feb 16; 11. PMID: 33584721    Free PMC article.
Review.
CCR8 blockade primes anti-tumor immunity through intratumoral regulatory T cells destabilization in muscle-invasive bladder cancer.
Tao Wang, Quan Zhou, +17 authors, Jiejie Xu.
Cancer Immunol Immunother, 2020 May 06; 69(9). PMID: 32367308
Systems biology analysis identifies TNFRSF9 as a functional marker of tumor-infiltrating regulatory T-cell enabling clinical outcome prediction in lung cancer.
Jae-Won Cho, Jimin Son, Sang-Jun Ha, Insuk Lee.
Comput Struct Biotechnol J, 2021 Feb 19; 19. PMID: 33598101    Free PMC article.
Common clonal origin of conventional T cells and induced regulatory T cells in breast cancer patients.
Maria Xydia, Raheleh Rahbari, +22 authors, Philipp Beckhove.
Nat Commun, 2021 Feb 20; 12(1). PMID: 33602930    Free PMC article.
Progress and Clinical Application of Single-Cell Transcriptional Sequencing Technology in Cancer Research.
Jian Liu, Tianmin Xu, +2 authors, Yan Zhang.
Front Oncol, 2021 Feb 23; 10. PMID: 33614479    Free PMC article.
Review.
Crosstalk between Macrophages, T Cells, and Iron Metabolism in Tumor Microenvironment.
Lesang Shen, Yunxiang Zhou, +6 authors, Jian Huang.
Oxid Med Cell Longev, 2021 Feb 26; 2021. PMID: 33628389    Free PMC article.
Review.
Screening and Identification of Four Prognostic Genes Related to Immune Infiltration and G-Protein Coupled Receptors Pathway in Lung Adenocarcinoma.
Yan Wang, Liwei Qiu, +3 authors, Feng Xu.
Front Oncol, 2021 Feb 26; 10. PMID: 33628734    Free PMC article.
Age-Related Gene Alteration in Naïve and Memory T cells Using Precise Age-Tracking Model.
Xiaofeng Yang, Xin Wang, +17 authors, Baojun Zhang.
Front Cell Dev Biol, 2021 Mar 02; 8. PMID: 33644036    Free PMC article.
Therapeutic depletion of CCR8+ tumor-infiltrating regulatory T cells elicits antitumor immunity and synergizes with anti-PD-1 therapy.
Helena Van Damme, Bruno Dombrecht, +26 authors, Jo Agnes Van Ginderachter.
J Immunother Cancer, 2021 Feb 17; 9(2). PMID: 33589525    Free PMC article.
Advances in Human Immune System Mouse Models for Personalized Treg-Based Immunotherapies.
Isabelle Serr, Maria Kral, Martin G Scherm, Carolin Daniel.
Front Immunol, 2021 Mar 09; 12. PMID: 33679808    Free PMC article.
Review.
The Impact of Tregs on the Anticancer Immunity and the Efficacy of Immune Checkpoint Inhibitor Therapies.
Jose M González-Navajas, Dengxia Denise Fan, +4 authors, Jongdae Lee.
Front Immunol, 2021 Mar 16; 12. PMID: 33717139    Free PMC article.
Review.
A Simplified Amino Acidic Alphabet to Unveil the T-Cells Receptors Antigens: A Computational Perspective.
Raffaele Iannuzzi, Grazisa Rossetti, +3 authors, Luca Mollica.
Front Chem, 2021 Mar 16; 9. PMID: 33718327    Free PMC article.
Critical Roles of Balanced T Helper 9 Cells and Regulatory T Cells in Allergic Airway Inflammation and Tumor Immunity.
Muhua Huang, Jingcheng Dong.
J Immunol Res, 2021 Mar 23; 2021. PMID: 33748292    Free PMC article.
Review.
Protective low-avidity anti-tumour CD8+ T cells are selectively attenuated by regulatory T cells.
Gessa Sugiyarto, David Prossor, +3 authors, Edward James.
Immunother Adv, 2021 Mar 23; 1(1). PMID: 33748824    Free PMC article.
Single-Cell Sequencing, an Advanced Technology in Lung Cancer Research.
Hao Wang, Die Meng, +14 authors, Yayi He.
Onco Targets Ther, 2021 Mar 25; 14. PMID: 33758510    Free PMC article.
Review.
Preoperative immune landscape predisposes adverse outcomes in hepatocellular carcinoma patients with liver transplantation.
Sang-Ho Yoon, Seo-Won Choi, +2 authors, Jin-Wu Nam.
NPJ Precis Oncol, 2021 Mar 28; 5(1). PMID: 33772139    Free PMC article.
Immunosuppressive Cell Subsets and Factors in Myeloid Leukemias.
Julian Swatler, Laura Turos-Korgul, Ewa Kozlowska, Katarzyna Piwocka.
Cancers (Basel), 2021 Apr 04; 13(6). PMID: 33801964    Free PMC article.
Review.
IL-1R2 expression in human gastric cancer and its clinical significance.
Maoling Yuan, Lei Wang, +4 authors, Jingting Jiang.
Biosci Rep, 2021 Mar 12; 41(3). PMID: 33704402    Free PMC article.
Improved understanding of gastrointestinal stromal tumors biology as a step for developing new diagnostic and therapeutic schemes.
Marta Magdalena Fudalej, Anna Maria Badowska-Kozakiewicz.
Oncol Lett, 2021 Apr 13; 21(5). PMID: 33841578    Free PMC article.
Review.
ADPRH is a prognosis-related biomarker and correlates with immune infiltrates in low grade glioma.
Chunyu Zhang, Long Wang, +7 authors, Daofeng Tian.
J Cancer, 2021 Apr 16; 12(10). PMID: 33854592    Free PMC article.
Immunotherapy for Hepatocellular Carcinoma: Current Limits and Prospects.
Cheng Zhong, Yirun Li, +5 authors, Hui Lin.
Front Oncol, 2021 Apr 16; 11. PMID: 33854960    Free PMC article.
Review.
Single-Cell Sequencing Reveals the Transcriptome and TCR Characteristics of pTregs and in vitro Expanded iTregs.
Zhenzhen Hui, Jiali Zhang, +5 authors, Xiubao Ren.
Front Immunol, 2021 Apr 20; 12. PMID: 33868236    Free PMC article.
Single-cell chromatin accessibility landscape identifies tissue repair program in human regulatory T cells.
Michael Delacher, Malte Simon, +26 authors, Markus Feuerer.
Immunity, 2021 Apr 01; 54(4). PMID: 33789089    Free PMC article.
Single-cell RNA-seq reveals dynamic change in tumor microenvironment during pancreatic ductal adenocarcinoma malignant progression.
Kai Chen, Qi Wang, +5 authors, Yinmo Yang.
EBioMedicine, 2021 Apr 06; 66. PMID: 33819739    Free PMC article.
Exhaustion in tumor-infiltrating Mucosal-Associated Invariant T (MAIT) cells from colon cancer patients.
William Rodin, Patrik Sundström, +5 authors, Marianne Quiding Järbrink.
Cancer Immunol Immunother, 2021 Apr 23; 70(12). PMID: 33885944    Free PMC article.
TNFR2: Role in Cancer Immunology and Immunotherapy.
Yang Yang, Md Sahidul Islam, Yuanjia Hu, Xin Chen.
Immunotargets Ther, 2021 Apr 29; 10. PMID: 33907692    Free PMC article.
Review.
GBP5 Repression Suppresses the Metastatic Potential and PD-L1 Expression in Triple-Negative Breast Cancer.
Shun-Wen Cheng, Po-Chih Chen, +3 authors, Yuan-Feng Lin.
Biomedicines, 2021 May 01; 9(4). PMID: 33916322    Free PMC article.
Hyperprogressive Disease: Main Features and Key Controversies.
Hugo Arasanz, Miren Zuazo, +15 authors, Ruth Vera.
Int J Mol Sci, 2021 May 01; 22(7). PMID: 33916696    Free PMC article.
Review.
Recruitment and Expansion of Tregs Cells in the Tumor Environment-How to Target Them?
Justine Cinier, Margaux Hubert, +5 authors, Christine Ménétrier-Caux.
Cancers (Basel), 2021 May 01; 13(8). PMID: 33924428    Free PMC article.
Review.
STARTRAC analyses of scRNAseq data from tumor models reveal T cell dynamics and therapeutic targets.
Dev Bhatt, Boxi Kang, +13 authors, Wenjun Ouyang.
J Exp Med, 2021 Apr 27; 218(6). PMID: 33900375    Free PMC article.
Conserved human effector Treg cell transcriptomic and epigenetic signature in arthritic joint inflammation.
Gerdien Mijnheer, Lisanne Lutter, +16 authors, Femke van Wijk.
Nat Commun, 2021 May 13; 12(1). PMID: 33976194    Free PMC article.
Clonally expanded EOMES+ Tr1-like cells in primary and metastatic tumors are associated with disease progression.
Raoul J P Bonnal, Grazisa Rossetti, +43 authors, Massimiliano Pagani.
Nat Immunol, 2021 May 22; 22(6). PMID: 34017124
Natural Killer Cell Interactions With Myeloid Derived Suppressor Cells in the Tumor Microenvironment and Implications for Cancer Immunotherapy.
Cristina Zalfa, Silke Paust.
Front Immunol, 2021 May 25; 12. PMID: 34025641    Free PMC article.
Review.
PP2A in LepR+ mesenchymal stem cells contributes to embryonic and postnatal endochondral ossification through Runx2 dephosphorylation.
Yu-Ting Yen, May Chien, Pei-Yi Wu, Shih-Chieh Hung.
Commun Biol, 2021 Jun 04; 4(1). PMID: 34079065    Free PMC article.
A risk model developed based on tumor microenvironment predicts overall survival and associates with tumor immunity of patients with lung adenocarcinoma.
Jie Wu, Lan Li, +4 authors, Bin Xu.
Oncogene, 2021 Jun 11; 40(26). PMID: 34108619
Peritumoral Tertiary Lymphoid Structures Correlate With Protective Immunity and Improved Prognosis in Patients With Hepatocellular Carcinoma.
Hui Li, Hailing Liu, +4 authors, Hong Wu.
Front Immunol, 2021 Jun 15; 12. PMID: 34122408    Free PMC article.
Intratumoral follicular regulatory T cells curtail anti-PD-1 treatment efficacy.
Simon Eschweiler, James Clarke, +14 authors, Pandurangan Vijayanand.
Nat Immunol, 2021 Jun 26; 22(8). PMID: 34168370    Free PMC article.
Single-cell analyses reveal suppressive tumor microenvironment of human colorectal cancer.
Yan Mei, Weiwei Xiao, +15 authors, Guangshuai Jia.
Clin Transl Med, 2021 Jun 30; 11(6). PMID: 34185431    Free PMC article.
Understanding the tumor microenvironment for effective immunotherapy.
Habib Sadeghi Rad, James Monkman, +4 authors, Arutha Kulasinghe.
Med Res Rev, 2020 Dec 06; 41(3). PMID: 33277742    Free PMC article.
Review.
G-quadruplex binders as cytostatic modulators of innate immune genes in cancer cells.
Giulia Miglietta, Marco Russo, Renée C Duardo, Giovanni Capranico.
Nucleic Acids Res, 2021 Jun 18; 49(12). PMID: 34139015    Free PMC article.
T Cell-Intrinsic CDK6 Is Dispensable for Anti-Viral and Anti-Tumor Responses In Vivo.
Klara Klein, Agnieszka Witalisz-Siepracka, +6 authors, Veronika Sexl.
Front Immunol, 2021 Jul 13; 12. PMID: 34248938    Free PMC article.
CCR8 marks highly suppressive Treg cells within tumours but is dispensable for their accumulation and suppressive function.
Sarah K Whiteside, Francis M Grant, +14 authors, Rahul Roychoudhuri.
Immunology, 2021 Apr 11; 163(4). PMID: 33838058    Free PMC article.
CD30+OX40+ Treg is associated with improved overall survival in colorectal cancer.
Jian Hang Lam, Michelle Hong, +10 authors, Tong Seng Lim.
Cancer Immunol Immunother, 2021 Feb 03; 70(8). PMID: 33527196    Free PMC article.
Identification of Prognostic miRNAs Associated With Immune Cell Tumor Infiltration Predictive of Clinical Outcomes in Patients With Non-Small Cell Lung Cancer.
Yuepeng Zhang, Kai Mi, +5 authors, Shoude Jin.
Front Oncol, 2021 Jul 20; 11. PMID: 34277450    Free PMC article.
Regulatory T-cell Transcriptomic Reprogramming Characterizes Adverse Events by Checkpoint Inhibitors in Solid Tumors.
Maria Grigoriou, Aggelos Banos, +13 authors, Panayotis Verginis.
Cancer Immunol Res, 2021 Apr 07; 9(7). PMID: 33820810    Free PMC article.
TIGIT, the Next Step Towards Successful Combination Immune Checkpoint Therapy in Cancer.
Zhouhong Ge, Maikel P Peppelenbosch, Dave Sprengers, Jaap Kwekkeboom.
Front Immunol, 2021 Aug 10; 12. PMID: 34367161    Free PMC article.
Review.
Intratumoral regulatory T cells from colon cancer patients comprise several activated effector populations.
Louis Szeponik, Filip Ahlmanner, +5 authors, Marianne Quiding-Järbrink.
BMC Immunol, 2021 Aug 20; 22(1). PMID: 34407765    Free PMC article.
PIP4Ks impact on PI3K, FOXP3, and UHRF1 signaling and modulate human regulatory T cell proliferation and immunosuppressive activity.
Alessandro Poli, Shidqiyyah Abdul-Hamid, +7 authors, Nullin Divecha.
Proc Natl Acad Sci U S A, 2021 Jul 28; 118(31). PMID: 34312224    Free PMC article.
Mechanisms of regulatory T cell infiltration in tumors: implications for innovative immune precision therapies.
Hiroyoshi Nishikawa, Shohei Koyama.
J Immunother Cancer, 2021 Aug 01; 9(7). PMID: 34330764    Free PMC article.
Review.
Natural killer cells and cytotoxic T lymphocytes are required to clear solid tumor in a patient-derived xenograft.
Duy Tri Le, Tridu R Huynh, +7 authors, Silke Paust.
JCI Insight, 2021 Jun 04; 6(13). PMID: 34081628    Free PMC article.
Chemokines and the immune response to cancer.
Aleksandra J Ozga, Melvyn T Chow, Andrew D Luster.
Immunity, 2021 Apr 12; 54(5). PMID: 33838745    Free PMC article.
Review.
GDF15 induces immunosuppression via CD48 on regulatory T cells in hepatocellular carcinoma.
Zhaowei Wang, Lei He, +19 authors, Meng Li.
J Immunother Cancer, 2021 Sep 08; 9(9). PMID: 34489334    Free PMC article.
Editorial: CD4+ T Cells in Cancer Immunotherapies.
José M González-Navajas, Eyad Elkord, Jongdae Lee.
Front Immunol, 2021 Sep 24; 12. PMID: 34552596    Free PMC article.
CD177 modulates the function and homeostasis of tumor-infiltrating regulatory T cells.
Myung-Chul Kim, Nicholas Borcherding, +32 authors, Weizhou Zhang.
Nat Commun, 2021 Oct 03; 12(1). PMID: 34599187    Free PMC article.
Profound Treg perturbations correlate with COVID-19 severity.
Silvia Galván-Peña, Juliette Leon, +16 authors, Christophe Benoist.
Proc Natl Acad Sci U S A, 2021 Aug 27; 118(37). PMID: 34433692    Free PMC article.
Layilin Anchors Regulatory T Cells in Skin.
Pooja Mehta, Victoire Gouirand, +20 authors, Michael D Rosenblum.
J Immunol, 2021 Sep 03; 207(7). PMID: 34470859    Free PMC article.
Effector T cell responses unleashed by regulatory T cell ablation exacerbate oral squamous cell carcinoma.
Jaime L Chao, Michael Korzinkin, +6 authors, Peter A Savage.
Cell Rep Med, 2021 Oct 09; 2(9). PMID: 34622236    Free PMC article.
Regulatory T-Cells and Multiple Myeloma: Implications in Tumor Immune Biology and Treatment.
Christina Hadjiaggelidou, Eirini Katodritou.
J Clin Med, 2021 Oct 14; 10(19). PMID: 34640606    Free PMC article.
Review.
Integrated analysis reveals distinct molecular, clinical, and immunological features of B7-H3 in acute myeloid leukemia.
Ling-Yi Zhang, Ye Jin, +9 authors, Jun Qian.
Cancer Med, 2021 Sep 26; 10(21). PMID: 34562306    Free PMC article.
mTOR-dependent translation drives tumor infiltrating CD8+ effector and CD4+ Treg cells expansion.
Benedetta De Ponte Conti, Annarita Miluzio, +3 authors, Sara Ricciardi.
Elife, 2021 Nov 18; 10. PMID: 34787568    Free PMC article.
Novel CircRNAs in Hub ceRNA Axis Regulate Gastric Cancer Prognosis and Microenvironment.
Xianghui Li, Zhiyan Li, +7 authors, Song Liu.
Front Med (Lausanne), 2021 Nov 26; 8. PMID: 34820403    Free PMC article.
Immune checkpoint inhibition for pancreatic ductal adenocarcinoma: limitations and prospects: a systematic review.
Hong-Bo Li, Zi-Han Yang, Qing-Qu Guo.
Cell Commun Signal, 2021 Nov 26; 19(1). PMID: 34819086    Free PMC article.
Review.
Chemokine Pathways in Cutaneous Melanoma: Their Modulation by Cancer and Exploitation by the Clinician.
Rebecca Adams, Bernhard Moser, Sophia N Karagiannis, Katie E Lacy.
Cancers (Basel), 2021 Nov 28; 13(22). PMID: 34830780    Free PMC article.
Review.
Pushing Past the Blockade: Advancements in T Cell-Based Cancer Immunotherapies.
Jessica Waibl Polania, Emily C Lerner, +2 authors, Peter E Fecci.
Front Immunol, 2021 Dec 07; 12. PMID: 34868044    Free PMC article.
Review.
Personalized Immunotherapy in Colorectal Cancers: Where Do We Stand?
Li-Feng Hu, Huan-Rong Lan, +2 authors, Ke-Tao Jin.
Front Oncol, 2021 Dec 11; 11. PMID: 34888246    Free PMC article.
Review.
Application and prospects of single cell sequencing in tumors.
Ruo Han Huang, Le Xin Wang, Jing He, Wen Gao.
Biomark Res, 2021 Dec 14; 9(1). PMID: 34895349    Free PMC article.
Review.
Expansion of tumor-associated Treg cells upon disruption of a CTLA-4-dependent feedback loop.
Francesco Marangoni, Ademi Zhakyp, +10 authors, Thorsten R Mempel.
Cell, 2021 Jun 23; 184(15). PMID: 34157302    Free PMC article.
Depletion of central memory CD8+ T cells might impede the antitumor therapeutic effect of Mogamulizumab.
Yuka Maeda, Hisashi Wada, +17 authors, Hiroyoshi Nishikawa.
Nat Commun, 2021 Dec 16; 12(1). PMID: 34907192    Free PMC article.
Single cell analysis of spondyloarthritis regulatory T cells identifies distinct synovial gene expression patterns and clonal fates.
Davide Simone, Frank Penkava, +3 authors, Paul Bowness.
Commun Biol, 2021 Dec 16; 4(1). PMID: 34907325    Free PMC article.
Breast cancer metastasis: immune profiling of lymph nodes reveals exhaustion of effector T cells and immunosuppression.
Inga Hansine Rye, Kanutte Huse, +9 authors, Hege G Russnes.
Mol Oncol, 2021 Jun 25; 16(1). PMID: 34165864    Free PMC article.
Tumor-Associated Regulatory T Cell Expression of LAIR2 Is Prognostic in Lung Adenocarcinoma.
Dalam Ly, Quan Li, +6 authors, Li Zhang.
Cancers (Basel), 2022 Jan 12; 14(1). PMID: 35008369    Free PMC article.
Spatial immune heterogeneity of hypoxia-induced exhausted features in high-grade glioma.
A-Reum Kim, Seong Jin Choi, +9 authors, Eui-Cheol Shin.
Oncoimmunology, 2022 Jan 18; 11(1). PMID: 35036078    Free PMC article.
Connecting blood and intratumoral Treg cell activity in predicting future relapse in breast cancer.
Lei Wang, Diana L Simons, +9 authors, Peter P Lee.
Nat Immunol, 2019 Jul 10; 20(9). PMID: 31285626    Free PMC article.
Highly Cited.
Single-Cell RNA Sequencing in Lung Cancer: Revealing Phenotype Shaping of Stromal Cells in the Microenvironment.
Jianhong Zhang, Chengyang Song, Ye Tian, Xueying Yang.
Front Immunol, 2022 Feb 08; 12. PMID: 35126365    Free PMC article.
Review.
Functional and molecular characterization of PD1+ tumor-infiltrating lymphocytes from lung cancer patients.
Jesse J Lipp, Limei Wang, +14 authors, Sean R R Hall.
Oncoimmunology, 2022 Feb 15; 11(1). PMID: 35154905    Free PMC article.
CCR8-targeted specific depletion of clonally expanded Treg cells in tumor tissues evokes potent tumor immunity with long-lasting memory.
Yujiro Kidani, Wataru Nogami, +39 authors, Shimon Sakaguchi.
Proc Natl Acad Sci U S A, 2022 Feb 11; 119(7). PMID: 35140181    Free PMC article.
Chemokine Receptor-Targeted Therapies: Special Case for CCR8.
Bernhard Moser.
Cancers (Basel), 2022 Feb 16; 14(3). PMID: 35158783    Free PMC article.
Review.
Negative Regulation of the IL-1 System by IL-1R2 and IL-1R8: Relevance in Pathophysiology and Disease.
Domenico Supino, Luna Minute, +3 authors, Cecilia Garlanda.
Front Immunol, 2022 Feb 26; 13. PMID: 35211118    Free PMC article.
Review.
4-1BBL-containing leukemic extracellular vesicles promote immunosuppressive effector regulatory T cells.
Julian Swatler, Laura Turos-Korgul, +16 authors, Katarzyna Piwocka.
Blood Adv, 2022 Feb 08; 6(6). PMID: 35130345    Free PMC article.
Tissue Resident Foxp3+ Regulatory T Cells: Sentinels and Saboteurs in Health and Disease.
Juyeun Lee, Dongkyun Kim, Booki Min.
Front Immunol, 2022 Apr 02; 13. PMID: 35359918    Free PMC article.
Review.
The impact of CCR8+ regulatory T cells on cytotoxic T cell function in human lung cancer.
Miya Haruna, Azumi Ueyama, +13 authors, Hisashi Wada.
Sci Rep, 2022 Apr 01; 12(1). PMID: 35354899    Free PMC article.
Prevalence of intratumoral regulatory T cells expressing neuropilin-1 is associated with poorer outcomes in patients with cancer.
Christopher A Chuckran, Anthony R Cillo, +26 authors, Dario A A Vignali.
Sci Transl Med, 2021 Dec 09; 13(623). PMID: 34878821    Free PMC article.
Direct targeting of FOXP3 in Tregs with AZD8701, a novel antisense oligonucleotide to relieve immunosuppression in cancer.
Alexey Revenko, Larissa S Carnevalli, +25 authors, A Robert MacLeod.
J Immunother Cancer, 2022 Apr 08; 10(4). PMID: 35387780    Free PMC article.
A Risk Model Developed Based on Necroptosis Predicts Overall Survival for Hepatocellular Carcinoma and Identification of Possible Therapeutic Drugs.
Zedong Li, Jianyu Fang, +5 authors, Yu Peng.
Front Immunol, 2022 Apr 16; 13. PMID: 35422802    Free PMC article.
Exploring the Mechanisms Underlying the Cardiotoxic Effects of Immune Checkpoint Inhibitor Therapies.
Daniel Ronen, Aseel Bsoul, +4 authors, Rabea Asleh.
Vaccines (Basel), 2022 Apr 24; 10(4). PMID: 35455289    Free PMC article.
Review.
Different subpopulations of regulatory T cells in human autoimmune disease, transplantation, and tumor immunity.
Zhongyi Jiang, Haitao Zhu, +4 authors, Futian Du.
MedComm (2020), 2022 Apr 28; 3(2). PMID: 35474948    Free PMC article.
Review.
Tumor-Associated Regulatory T Cells in Non-Small-Cell Lung Cancer: Current Advances and Future Perspectives.
Jiaqi Liang, Guoshu Bi, +3 authors, Qun Wang.
J Immunol Res, 2022 May 03; 2022. PMID: 35497874    Free PMC article.
Review.
Landscape of helper and regulatory antitumour CD4+ T cells in melanoma.
Giacomo Oliveira, Kari Stromhaug, +24 authors, Catherine J Wu.
Nature, 2022 May 05; 605(7910). PMID: 35508657
Identification of Tumor Microenvironment and DNA Methylation-Related Prognostic Signature for Predicting Clinical Outcomes and Therapeutic Responses in Cervical Cancer.
Bangquan Liu, Jiabao Zhai, +6 authors, Fubin Zhang.
Front Mol Biosci, 2022 May 07; 9. PMID: 35517856    Free PMC article.
Single-cell landscape of immunocytes in patients with extrahepatic cholangiocarcinoma.
Lei Xu, Yun Lu, +5 authors, Jianming Wang.
J Transl Med, 2022 May 14; 20(1). PMID: 35562760    Free PMC article.