Review
. 2018 Feb; 2017:5458178.
doi: 10.1155/2017/5458178.

Phenotypic and Functional Properties of Tumor-Infiltrating Regulatory T Cells

Gap Ryol Lee 1 
Affiliations
  • PMID: 29463952
  •     103 References
  •     11 citations

Abstract

Regulatory T (Treg) cells maintain immune homeostasis by suppressing excessive immune responses. Treg cells induce tolerance against self- and foreign antigens, thus preventing autoimmunity, allergy, graft rejection, and fetus rejection during pregnancy. However, Treg cells also infiltrate into tumors and inhibit antitumor immune responses, thus inhibiting anticancer therapy. Depleting whole Treg cell populations in the body to enhance anticancer treatments will produce deleterious autoimmune diseases. Therefore, understanding the precise nature of tumor-infiltrating Treg cells is essential for effectively targeting Treg cells in tumors. This review summarizes recent results relating to Treg cells in the tumor microenvironment, with particular emphasis on their accumulation, phenotypic, and functional properties, and targeting to enhance the efficacy of anticancer treatment.

Nivolumab plus ipilimumab in advanced melanoma.
Jedd D Wolchok, Harriet Kluger, +21 authors, Mario Sznol.
N Engl J Med, 2013 Jun 04; 369(2). PMID: 23724867    Free PMC article.
Highly Cited.
Microenvironmental regulation of metastasis.
Johanna A Joyce, Jeffrey W Pollard.
Nat Rev Cancer, 2009 Mar 13; 9(4). PMID: 19279573    Free PMC article.
Highly Cited. Review.
Regulatory T-cell trafficking: from thymic development to tumor-induced immune suppression.
Adam W Mailloux, M Rita I Young.
Crit Rev Immunol, 2010 Nov 19; 30(5). PMID: 21083525    Free PMC article.
Review.
Modulation of lymphocyte regulation for cancer therapy: a phase II trial of tremelimumab in advanced gastric and esophageal adenocarcinoma.
Christy Ralph, Eyad Elkord, +5 authors, Fiona C Thistlethwaite.
Clin Cancer Res, 2010 Feb 25; 16(5). PMID: 20179239
Reversal of tumor-induced dendritic cell paralysis by CpG immunostimulatory oligonucleotide and anti-interleukin 10 receptor antibody.
Alain P Vicari, Claudia Chiodoni, +10 authors, Christophe Caux.
J Exp Med, 2002 Aug 21; 196(4). PMID: 12186845    Free PMC article.
IDO expression in brain tumors increases the recruitment of regulatory T cells and negatively impacts survival.
Derek A Wainwright, Irina V Balyasnikova, +6 authors, Maciej S Lesniak.
Clin Cancer Res, 2012 Aug 31; 18(22). PMID: 22932670    Free PMC article.
Highly Cited.
Instability of Helios-deficient Tregs is associated with conversion to a T-effector phenotype and enhanced antitumor immunity.
Hidetoshi Nakagawa, Jessica M Sido, +3 authors, Hye-Jung Kim.
Proc Natl Acad Sci U S A, 2016 May 18; 113(22). PMID: 27185917    Free PMC article.
The role of regulatory T cells in cancer immunology.
Theresa L Whiteside.
Immunotargets Ther, 2015 Jan 01; 4. PMID: 27471721    Free PMC article.
Review.
Regulatory T cells recruited through CCL22/CCR4 are selectively activated in lymphoid infiltrates surrounding primary breast tumors and lead to an adverse clinical outcome.
Michael Gobert, Isabelle Treilleux, +15 authors, Christine Ménétrier-Caux.
Cancer Res, 2009 Feb 27; 69(5). PMID: 19244125
Highly Cited.
Home sweet home: the tumor microenvironment as a haven for regulatory T cells.
Beatrice Ondondo, Emma Jones, Andrew Godkin, Awen Gallimore.
Front Immunol, 2013 Jul 23; 4. PMID: 23874342    Free PMC article.
Two distinct mechanisms of augmented antitumor activity by modulation of immunostimulatory/inhibitory signals.
Jun Mitsui, Hiroyoshi Nishikawa, +9 authors, Hiroshi Shiku.
Clin Cancer Res, 2010 May 13; 16(10). PMID: 20460483
The combined effects of tryptophan starvation and tryptophan catabolites down-regulate T cell receptor zeta-chain and induce a regulatory phenotype in naive T cells.
Francesca Fallarino, Ursula Grohmann, +10 authors, Paolo Puccetti.
J Immunol, 2006 May 20; 176(11). PMID: 16709834
Highly Cited.
Foxp3 programs the development and function of CD4+CD25+ regulatory T cells.
Jason D Fontenot, Marc A Gavin, Alexander Y Rudensky.
Nat Immunol, 2003 Mar 04; 4(4). PMID: 12612578
Highly Cited.
Aire-dependent thymic development of tumor-associated regulatory T cells.
Sven Malchow, Daniel S Leventhal, +9 authors, Peter A Savage.
Science, 2013 Mar 09; 339(6124). PMID: 23471412    Free PMC article.
Highly Cited.
Immune-mediated eradication of tumors through the blockade of transforming growth factor-beta signaling in T cells.
L Gorelik, R A Flavell.
Nat Med, 2001 Oct 09; 7(10). PMID: 11590434
Highly Cited.
Two FOXP3(+)CD4(+) T cell subpopulations distinctly control the prognosis of colorectal cancers.
Takuro Saito, Hiroyoshi Nishikawa, +19 authors, Shimon Sakaguchi.
Nat Med, 2016 Apr 26; 22(6). PMID: 27111280
Highly Cited.
Natural regulatory T cells and de novo-induced regulatory T cells contribute independently to tumor-specific tolerance.
Gang Zhou, Hyam I Levitsky.
J Immunol, 2007 Feb 06; 178(4). PMID: 17277120
IL10 and PD-1 Cooperate to Limit the Activity of Tumor-Specific CD8+ T Cells.
Zhaojun Sun, Julien Fourcade, +4 authors, Hassane M Zarour.
Cancer Res, 2015 Feb 28; 75(8). PMID: 25720800    Free PMC article.
Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival.
Tyler J Curiel, George Coukos, +18 authors, Weiping Zou.
Nat Med, 2004 Aug 24; 10(9). PMID: 15322536
Highly Cited.
Cancer acidity: An ultimate frontier of tumor immune escape and a novel target of immunomodulation.
Veronica Huber, Chiara Camisaschi, +7 authors, Licia Rivoltini.
Semin Cancer Biol, 2017 Mar 08; 43. PMID: 28267587
Highly Cited. Review.
Comparative analysis of regulatory and effector T cells in progressively growing versus rejecting tumors of similar origins.
Jack D Bui, Ravindra Uppaluri, Chyi-Song Hsieh, Robert D Schreiber.
Cancer Res, 2006 Jul 20; 66(14). PMID: 16849580
Specific recruitment of CC chemokine receptor 4-positive regulatory T cells in Hodgkin lymphoma fosters immune privilege.
Takashi Ishida, Toshihiko Ishii, +5 authors, Ryuzo Ueda.
Cancer Res, 2006 Jun 03; 66(11). PMID: 16740709
Ex vivo analysis of pancreatic cancer-infiltrating T lymphocytes reveals that ENO-specific Tregs accumulate in tumor tissue and inhibit Th1/Th17 effector cell functions.
Amedeo Amedei, Elena Niccolai, +10 authors, Mario Milco D'Elios.
Cancer Immunol Immunother, 2013 May 04; 62(7). PMID: 23640603
An increased abundance of tumor-infiltrating regulatory T cells is correlated with the progression and prognosis of pancreatic ductal adenocarcinoma.
Yichen Tang, Xuejun Xu, +6 authors, Huaizhi Wang.
PLoS One, 2014 Mar 19; 9(3). PMID: 24637664    Free PMC article.
Highly Cited.
Stromal regulatory T-cells are associated with a favourable prognosis in gastric cancer of the cardia.
Matthias Haas, Arno Dimmler, +3 authors, Luitpold V Distel.
BMC Gastroenterol, 2009 Sep 08; 9. PMID: 19732435    Free PMC article.
Stability and function of regulatory T cells is maintained by a neuropilin-1-semaphorin-4a axis.
Greg M Delgoffe, Seng-Ryong Woo, +9 authors, Dario A A Vignali.
Nature, 2013 Aug 06; 501(7466). PMID: 23913274    Free PMC article.
Highly Cited.
Intratumoral CD4+CD25+ regulatory T-cell-mediated suppression of infiltrating CD4+ T cells in B-cell non-Hodgkin lymphoma.
Zhi-Zhang Yang, Anne J Novak, +2 authors, Stephen M Ansell.
Blood, 2006 Jan 13; 107(9). PMID: 16403912    Free PMC article.
Highly Cited.
CTLA4 blockade expands FoxP3+ regulatory and activated effector CD4+ T cells in a dose-dependent fashion.
Brian Kavanagh, Shaun O'Brien, +6 authors, Lawrence Fong.
Blood, 2008 Jun 05; 112(4). PMID: 18523152    Free PMC article.
CXCR3+ T regulatory cells selectively accumulate in human ovarian carcinomas to limit type I immunity.
Nassima Redjimi, Caroline Raffin, +5 authors, Maha Ayyoub.
Cancer Res, 2012 Jul 17; 72(17). PMID: 22798340
Foxp3 Reprograms T Cell Metabolism to Function in Low-Glucose, High-Lactate Environments.
Alessia Angelin, Luis Gil-de-Gómez, +17 authors, Ulf H Beier.
Cell Metab, 2017 Apr 19; 25(6). PMID: 28416194    Free PMC article.
Highly Cited.
CTLA-4 and PD-1 Pathways: Similarities, Differences, and Implications of Their Inhibition.
Elizabeth I Buchbinder, Anupam Desai.
Am J Clin Oncol, 2015 Nov 13; 39(1). PMID: 26558876    Free PMC article.
Highly Cited. Review.
NF-κB c-Rel Is Crucial for the Regulatory T Cell Immune Checkpoint in Cancer.
Yenkel Grinberg-Bleyer, Hyunju Oh, +7 authors, Sankar Ghosh.
Cell, 2017 Sep 09; 170(6). PMID: 28886380    Free PMC article.
Highly Cited.
An interaction between kynurenine and the aryl hydrocarbon receptor can generate regulatory T cells.
Joshua D Mezrich, John H Fechner, +3 authors, Christopher A Bradfield.
J Immunol, 2010 Aug 20; 185(6). PMID: 20720200    Free PMC article.
Highly Cited.
A pilot study of IL-2Rα blockade during lymphopenia depletes regulatory T-cells and correlates with enhanced immunity in patients with glioblastoma.
John H Sampson, Robert J Schmittling, +13 authors, Duane A Mitchell.
PLoS One, 2012 Mar 03; 7(2). PMID: 22383993    Free PMC article.
Treg depletion potentiates checkpoint inhibition in claudin-low breast cancer.
Nicholas A Taylor, Sarah C Vick, +10 authors, Jonathan S Serody.
J Clin Invest, 2017 Aug 22; 127(9). PMID: 28825599    Free PMC article.
Highly Cited.
How regulatory T cells work.
Dario A A Vignali, Lauren W Collison, Creg J Workman.
Nat Rev Immunol, 2008 Jun 21; 8(7). PMID: 18566595    Free PMC article.
Highly Cited. Review.
PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma.
Stephen M Ansell, Alexander M Lesokhin, +16 authors, Philippe Armand.
N Engl J Med, 2014 Dec 09; 372(4). PMID: 25482239    Free PMC article.
Highly Cited.
Ipilimumab increases activated T cells and enhances humoral immunity in patients with advanced melanoma.
Jeffrey S Weber, Omid Hamid, +5 authors, David Berman.
J Immunother, 2011 Dec 02; 35(1). PMID: 22130166
The immunosuppressive tumour network: myeloid-derived suppressor cells, regulatory T cells and natural killer T cells.
Dennis Lindau, Paul Gielen, +2 authors, Gosse J Adema.
Immunology, 2012 Dec 12; 138(2). PMID: 23216602    Free PMC article.
Highly Cited. Review.
The functional impairment of HCC-infiltrating γδ T cells, partially mediated by regulatory T cells in a TGFβ- and IL-10-dependent manner.
Yong Yi, Hong-Wei He, +7 authors, Shuang-Jian Qiu.
J Hepatol, 2012 Dec 25; 58(5). PMID: 23262246
Highly prevalent colorectal cancer-infiltrating LAP⁺ Foxp3⁻ T cells exhibit more potent immunosuppressive activity than Foxp3⁺ regulatory T cells.
M Scurr, K Ladell, +10 authors, A Godkin.
Mucosal Immunol, 2013 Sep 26; 7(2). PMID: 24064667    Free PMC article.
Tim-3 expression defines regulatory T cells in human tumors.
Jing Yan, Yi Zhang, +3 authors, Limin Zheng.
PLoS One, 2013 Mar 26; 8(3). PMID: 23526963    Free PMC article.
CD25 blockade depletes and selectively reprograms regulatory T cells in concert with immunotherapy in cancer patients.
Andrew J Rech, Rosemarie Mick, +13 authors, Robert H Vonderheide.
Sci Transl Med, 2012 May 18; 4(134). PMID: 22593175    Free PMC article.
Highly Cited.
CTLA-4-Ig regulates tryptophan catabolism in vivo.
Ursula Grohmann, Ciriana Orabona, +8 authors, Paolo Puccetti.
Nat Immunol, 2002 Oct 09; 3(11). PMID: 12368911
Highly Cited.
Blockade of TGF-beta inhibits mammary tumor cell viability, migration, and metastases.
Rebecca S Muraoka, Nancy Dumont, +9 authors, Carlos L Arteaga.
J Clin Invest, 2002 Jun 19; 109(12). PMID: 12070302    Free PMC article.
Highly Cited.
Metabolic Regulation of Tregs in Cancer: Opportunities for Immunotherapy.
Haiping Wang, Fabien Franco, Ping-Chih Ho.
Trends Cancer, 2017 Aug 07; 3(8). PMID: 28780935
Review.
Lactate Wreaks Havoc on Tumor-Infiltrating T and NK Cells.
Kristen E N Scott, John L Cleveland.
Cell Metab, 2016 Nov 10; 24(5). PMID: 27829133
Optimal population of FoxP3+ T cells in tumors requires an antigen priming-dependent trafficking receptor switch.
Chuanwu Wang, Jee H Lee, Chang H Kim.
PLoS One, 2012 Feb 01; 7(1). PMID: 22292042    Free PMC article.
Phosphoenolpyruvate Is a Metabolic Checkpoint of Anti-tumor T Cell Responses.
Ping-Chih Ho, Jessica Dauz Bihuniak, +15 authors, Susan M Kaech.
Cell, 2015 Sep 01; 162(6). PMID: 26321681    Free PMC article.
Highly Cited.
Disruption of CCR5-dependent homing of regulatory T cells inhibits tumor growth in a murine model of pancreatic cancer.
Marcus C B Tan, Peter S Goedegebuure, +6 authors, David C Linehan.
J Immunol, 2009 Jan 22; 182(3). PMID: 19155524    Free PMC article.
Highly Cited.
Increased proportion of FoxP3+ regulatory T cells in tumor infiltrating lymphocytes is associated with tumor recurrence and reduced survival in patients with glioblastoma.
Elias J Sayour, Pat McLendon, +5 authors, Duane A Mitchell.
Cancer Immunol Immunother, 2015 Jan 04; 64(4). PMID: 25555571    Free PMC article.
OX40 triggering blocks suppression by regulatory T cells and facilitates tumor rejection.
Silvia Piconese, Barbara Valzasina, Mario P Colombo.
J Exp Med, 2008 Mar 26; 205(4). PMID: 18362171    Free PMC article.
Highly Cited.
Control of regulatory T cell development by the transcription factor Foxp3.
Shohei Hori, Takashi Nomura, Shimon Sakaguchi.
Science, 2003 Jan 11; 299(5609). PMID: 12522256
Highly Cited.
Inhibitory effect of tumor cell-derived lactic acid on human T cells.
Karin Fischer, Petra Hoffmann, +14 authors, Marina Kreutz.
Blood, 2007 Jan 27; 109(9). PMID: 17255361
Highly Cited.
Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells.
Jens Dannull, Zhen Su, +8 authors, Johannes Vieweg.
J Clin Invest, 2005 Nov 26; 115(12). PMID: 16308572    Free PMC article.
Highly Cited.
Dynamic Treg interactions with intratumoral APCs promote local CTL dysfunction.
Christian A Bauer, Edward Y Kim, +3 authors, Thorsten R Mempel.
J Clin Invest, 2014 May 09; 124(6). PMID: 24812664    Free PMC article.
Highly Cited.
Activated tumor-infiltrating CD4+ regulatory T cells restrain antitumor immunity in patients with primary or metastatic liver cancer.
Alexander Pedroza-Gonzalez, Cornelis Verhoef, +5 authors, Dave Sprengers.
Hepatology, 2012 Aug 23; 57(1). PMID: 22911397
Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors.
Frederick Arce Vargas, Andrew J S Furness, +29 authors, Sergio A Quezada.
Immunity, 2017 Apr 16; 46(4). PMID: 28410988    Free PMC article.
Highly Cited.
Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab.
Suzanne L Topalian, Mario Sznol, +18 authors, F Stephen Hodi.
J Clin Oncol, 2014 Mar 05; 32(10). PMID: 24590637    Free PMC article.
Highly Cited.
A special population of regulatory T cells potentiates muscle repair.
Dalia Burzyn, Wilson Kuswanto, +8 authors, Diane Mathis.
Cell, 2013 Dec 10; 155(6). PMID: 24315098    Free PMC article.
Highly Cited.
Tumor-infiltrating FOXP3+ T regulatory cells show strong prognostic significance in colorectal cancer.
Paul Salama, Michael Phillips, +5 authors, Barry Iacopetta.
J Clin Oncol, 2008 Dec 10; 27(2). PMID: 19064967
Highly Cited.
Metabolic Competition in the Tumor Microenvironment Is a Driver of Cancer Progression.
Chih-Hao Chang, Jing Qiu, +11 authors, Erika L Pearce.
Cell, 2015 Sep 01; 162(6). PMID: 26321679    Free PMC article.
Highly Cited.
Analysis of the cellular mechanism of antitumor responses and autoimmunity in patients treated with CTLA-4 blockade.
Ajay V Maker, Peter Attia, Steven A Rosenberg.
J Immunol, 2005 Nov 23; 175(11). PMID: 16301685    Free PMC article.
Prognostic value of tumor-infiltrating FoxP3+ regulatory T cells in cancers: a systematic review and meta-analysis.
Bin Shang, Yao Liu, Shu-juan Jiang, Yi Liu.
Sci Rep, 2015 Oct 16; 5. PMID: 26462617    Free PMC article.
Highly Cited. Systematic Review.
A CCR4 antagonist combined with vaccines induces antigen-specific CD8+ T cells and tumor immunity against self antigens.
Helene Pere, Yves Montier, +20 authors, Eric Tartour.
Blood, 2011 Sep 13; 118(18). PMID: 21908423
Prognostic value of tumor-infiltrating CD4+ T-cell subpopulations in head and neck cancers.
Cécile Badoual, Stéphane Hans, +9 authors, Eric Tartour.
Clin Cancer Res, 2006 Jan 24; 12(2). PMID: 16428488
Highly Cited.
Metabolic regulation of T lymphocytes.
Nancie J MacIver, Ryan D Michalek, Jeffrey C Rathmell.
Annu Rev Immunol, 2013 Jan 10; 31. PMID: 23298210    Free PMC article.
Highly Cited. Review.
Analysis of the T-cell receptor repertoires of tumor-infiltrating conventional and regulatory T cells reveals no evidence for conversion in carcinogen-induced tumors.
James P Hindley, Cristina Ferreira, +9 authors, Awen Gallimore.
Cancer Res, 2010 Dec 16; 71(3). PMID: 21156649    Free PMC article.
Interferon-γ Drives Treg Fragility to Promote Anti-tumor Immunity.
Abigail E Overacre-Delgoffe, Maria Chikina, +15 authors, Dario A A Vignali.
Cell, 2017 May 30; 169(6). PMID: 28552348    Free PMC article.
Highly Cited.
Prognostic significance of tumor-infiltrating T-lymphocytes in primary and metastatic lesions of advanced stage ovarian cancer.
Ninke Leffers, Marloes J M Gooden, +7 authors, Hans W Nijman.
Cancer Immunol Immunother, 2008 Sep 16; 58(3). PMID: 18791714
Highly Cited.
Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets.
Ryan D Michalek, Valerie A Gerriets, +6 authors, Jeffrey C Rathmell.
J Immunol, 2011 Feb 15; 186(6). PMID: 21317389    Free PMC article.
Highly Cited.
Inability of a fusion protein of IL-2 and diphtheria toxin (Denileukin Diftitox, DAB389IL-2, ONTAK) to eliminate regulatory T lymphocytes in patients with melanoma.
Peter Attia, Ajay V Maker, +2 authors, Steven A Rosenberg.
J Immunother, 2005 Oct 15; 28(6). PMID: 16224276    Free PMC article.
A pilot study of CTLA-4 blockade after cancer vaccine failure in patients with advanced malignancy.
Deirdre O'Mahony, John C Morris, +16 authors, John E Janik.
Clin Cancer Res, 2007 Feb 10; 13(3). PMID: 17289891
Prognostic potential of FOXP3 expression in non-small cell lung cancer cells combined with tumor-infiltrating regulatory T cells.
Hiroyuki Tao, Yusuke Mimura, +7 authors, Hiroshi Ueoka.
Lung Cancer, 2011 Jul 02; 75(1). PMID: 21719142
Modulation of tryptophan catabolism by human leukemic cells results in the conversion of CD25- into CD25+ T regulatory cells.
Antonio Curti, Simona Pandolfi, +13 authors, Roberto M Lemoli.
Blood, 2006 Dec 14; 109(7). PMID: 17164341
Highly Cited.
Inactivation of PI(3)K p110δ breaks regulatory T-cell-mediated immune tolerance to cancer.
Khaled Ali, Dalya R Soond, +11 authors, Bart Vanhaesebroeck.
Nature, 2014 Jun 12; 510(7505). PMID: 24919154    Free PMC article.
Highly Cited.
T regulatory cells, the evolution of targeted immunotherapy.
S Nizar, B Meyer, +2 authors, A Dalgleish.
Biochim Biophys Acta, 2010 Mar 02; 1806(1). PMID: 20188145
Review.
On being less tolerant: enhanced cancer immunosurveillance enabled by targeting checkpoints and agonists of T cell activation.
Alexander M Lesokhin, Margaret K Callahan, Michael A Postow, Jedd D Wolchok.
Sci Transl Med, 2015 Mar 27; 7(280). PMID: 25810313
Highly Cited. Review.
Cancer and inflammation: an old intuition with rapidly evolving new concepts.
Giorgio Trinchieri.
Annu Rev Immunol, 2012 Jan 10; 30. PMID: 22224761
Highly Cited. Review.
Neuropilin 1 is expressed on thymus-derived natural regulatory T cells, but not mucosa-generated induced Foxp3+ T reg cells.
Jonathan M Weiss, Angelina M Bilate, +17 authors, Juan J Lafaille.
J Exp Med, 2012 Sep 12; 209(10). PMID: 22966001    Free PMC article.
Highly Cited.
Transcriptional Landscape of Human Tissue Lymphocytes Unveils Uniqueness of Tumor-Infiltrating T Regulatory Cells.
Marco De Simone, Alberto Arrigoni, +28 authors, Massimiliano Pagani.
Immunity, 2016 Nov 17; 45(5). PMID: 27851914    Free PMC article.
Highly Cited.
Mechanisms and functional significance of tumour-induced dendritic-cell defects.
Dmitry Gabrilovich.
Nat Rev Immunol, 2004 Dec 02; 4(12). PMID: 15573129
Highly Cited. Review.
The T-cell receptor repertoire of tumor-infiltrating regulatory T lymphocytes is skewed toward public sequences.
Alexander Sainz-Perez, Annick Lim, Brigitte Lemercier, Claude Leclerc.
Cancer Res, 2012 May 11; 72(14). PMID: 22573714
Dendritic cell vaccination in combination with anti-CD25 monoclonal antibody treatment: a phase I/II study in metastatic melanoma patients.
Joannes F M Jacobs, Cornelis J A Punt, +8 authors, Gosse J Adema.
Clin Cancer Res, 2010 Aug 26; 16(20). PMID: 20736326
Regulatory T Cells in the Tumor Microenvironment and Cancer Progression: Role and Therapeutic Targeting.
Belal Chaudhary, Eyad Elkord.
Vaccines (Basel), 2016 Aug 12; 4(3). PMID: 27509527    Free PMC article.
Highly Cited. Review.
Treatment of advanced tumors with agonistic anti-GITR mAb and its effects on tumor-infiltrating Foxp3+CD25+CD4+ regulatory T cells.
Kuibeom Ko, Sayuri Yamazaki, +7 authors, Shimon Sakaguchi.
J Exp Med, 2005 Sep 28; 202(7). PMID: 16186187    Free PMC article.
Highly Cited.
Comparative analyses of regulatory T cell subsets in patients with hepatocellular carcinoma: a crucial role of CD25(-) FOXP3(-) T cells.
Naruyasu Kakita, Tatsuya Kanto, +10 authors, Norio Hayashi.
Int J Cancer, 2012 Mar 16; 131(11). PMID: 22419479
Ovarian carcinoma-infiltrating regulatory T cells were more potent suppressors of CD8(+) T cell inflammation than their peripheral counterparts, a function dependent on TIM3 expression.
Meimei Bu, Yizhen Shen, +4 authors, Yan Cai.
Tumour Biol, 2015 Oct 21; 37(3). PMID: 26482613
Increase in activated Treg in TIL in lung cancer and in vitro depletion of Treg by ADCC using an antihuman CCR4 mAb (KM2760).
Koji Kurose, Yoshihiro Ohue, +7 authors, Eiichi Nakayama.
J Thorac Oncol, 2014 Oct 18; 10(1). PMID: 25325779
FOXP3+ lymphocyte density in pancreatic cancer correlates with lymph node metastasis.
Yongjian Jiang, Zunguo Du, +5 authors, Deliang Fu.
PLoS One, 2014 Sep 06; 9(9). PMID: 25191901    Free PMC article.
Tumour hypoxia promotes tolerance and angiogenesis via CCL28 and T(reg) cells.
Andrea Facciabene, Xiaohui Peng, +8 authors, George Coukos.
Nature, 2011 Jul 15; 475(7355). PMID: 21753853
Highly Cited.
The immune contexture in cancer prognosis and treatment.
Wolf H Fridman, Laurence Zitvogel, Catherine Sautès-Fridman, Guido Kroemer.
Nat Rev Clin Oncol, 2017 Jul 26; 14(12). PMID: 28741618
Highly Cited. Review.
Comprehensive analysis of current approaches to inhibit regulatory T cells in cancer.
Helene Pere, Corinne Tanchot, +17 authors, Eric Tartour.
Oncoimmunology, 2012 Jun 28; 1(3). PMID: 22737608    Free PMC article.
Regulatory T Cells Exhibit Distinct Features in Human Breast Cancer.
George Plitas, Catherine Konopacki, +5 authors, Alexander Y Rudensky.
Immunity, 2016 Nov 17; 45(5). PMID: 27851913    Free PMC article.
Highly Cited.
Immune Checkpoint Blockade in Cancer Therapy.
Michael A Postow, Margaret K Callahan, Jedd D Wolchok.
J Clin Oncol, 2015 Jan 22; 33(17). PMID: 25605845    Free PMC article.
Highly Cited. Review.
Graded Foxo1 activity in Treg cells differentiates tumour immunity from spontaneous autoimmunity.
Chong T Luo, Will Liao, +2 authors, Ming O Li.
Nature, 2016 Jan 21; 529(7587). PMID: 26789248    Free PMC article.
Highly Cited.
Regulatory circuits of T cell function in cancer.
Daniel E Speiser, Ping-Chih Ho, Grégory Verdeil.
Nat Rev Immunol, 2016 Aug 17; 16(10). PMID: 27526640
Highly Cited. Review.
Interleukin-35 Limits Anti-Tumor Immunity.
Meghan E Turnis, Deepali V Sawant, +7 authors, Dario A A Vignali.
Immunity, 2016 Feb 14; 44(2). PMID: 26872697    Free PMC article.
Highly Cited.
Defucosylated anti-CCR4 monoclonal antibody (KW-0761) for relapsed adult T-cell leukemia-lymphoma: a multicenter phase II study.
Takashi Ishida, Tatsuro Joh, +17 authors, Ryuzo Ueda.
J Clin Oncol, 2012 Feb 09; 30(8). PMID: 22312108
Highly Cited.
Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma.
Tyler R Simpson, Fubin Li, +11 authors, Sergio A Quezada.
J Exp Med, 2013 Jul 31; 210(9). PMID: 23897981    Free PMC article.
Highly Cited.
The prognostic value of FoxP3+ tumor-infiltrating lymphocytes in cancer: a critical review of the literature.
Ronald J deLeeuw, Sara E Kost, Juzer A Kakal, Brad H Nelson.
Clin Cancer Res, 2012 Apr 19; 18(11). PMID: 22510350
Highly Cited. Systematic Review.
Accessories to the crime: functions of cells recruited to the tumor microenvironment.
Douglas Hanahan, Lisa M Coussens.
Cancer Cell, 2012 Mar 24; 21(3). PMID: 22439926
Highly Cited. Review.
Prognostic role of FOXP3+ regulatory T cells infiltrating human carcinomas: the paradox of colorectal cancer.
Sylvain Ladoire, François Martin, François Ghiringhelli.
Cancer Immunol Immunother, 2011 Jun 07; 60(7). PMID: 21644034
Highly Cited. Review.
Rationale for Combining Bispecific T Cell Activating Antibodies With Checkpoint Blockade for Cancer Therapy.
Sebastian Kobold, Stanislav Pantelyushin, Felicitas Rataj, Johannes Vom Berg.
Front Oncol, 2018 Aug 10; 8. PMID: 30090763    Free PMC article.
Review.
Effect of Stromal Cells in Tumor Microenvironment on Metastasis Initiation.
Sen Guo, Chu-Xia Deng.
Int J Biol Sci, 2018 Dec 27; 14(14). PMID: 30585271    Free PMC article.
Review.
Tumor Lymphatic Function Regulates Tumor Inflammatory and Immunosuppressive Microenvironments.
Raghu P Kataru, Catherine L Ly, +6 authors, Babak J Mehrara.
Cancer Immunol Res, 2019 Jun 13; 7(8). PMID: 31186247    Free PMC article.
Relevance of immune cell and tumor microenvironment imaging in the new era of immunotherapy.
Filippo Galli, Jesus Vera Aguilera, +3 authors, Alberto Signore.
J Exp Clin Cancer Res, 2020 May 20; 39(1). PMID: 32423420    Free PMC article.
Review.
Intratumoral Versus Circulating Lymphoid Cells as Predictive Biomarkers in Lung Cancer Patients Treated with Immune Checkpoint Inhibitors: Is the Easiest Path the Best One?
Marta Gascón, Dolores Isla, +10 authors, Luis Martínez-Lostao.
Cells, 2020 Jun 26; 9(6). PMID: 32580514    Free PMC article.
Review.
Analysis and Augmentation of the Immunologic Bystander Effects of CAR T Cell Therapy in a Syngeneic Mouse Cancer Model.
Astero Klampatsa, Michael S Leibowitz, +3 authors, Steven M Albelda.
Mol Ther Oncolytics, 2020 Aug 18; 18. PMID: 32802940    Free PMC article.
Prognostic value of tumor-infiltrating lymphocytes in melanoma: a systematic review and meta-analysis.
Qiaofen Fu, Nan Chen, +9 authors, Gaofeng Li.
Oncoimmunology, 2019 May 31; 8(7). PMID: 31143514    Free PMC article.
Highly Cited. Review.
Significance of Tumor Mutation Burden in Immune Infiltration and Prognosis in Cutaneous Melanoma.
Kai Kang, Fucun Xie, +2 authors, Xiang Wang.
Front Oncol, 2020 Oct 20; 10. PMID: 33072607    Free PMC article.
Research advances of secretory proteins in malignant tumors.
Na Zhang, Jiajie Hao, Yan Cai, Mingrong Wang.
Chin J Cancer Res, 2021 Mar 13; 33(1). PMID: 33707934    Free PMC article.
A Novel CAR Expressing NK Cell Targeting CD25 With the Prospect of Overcoming Immune Escape Mechanism in Cancers.
Moein Dehbashi, Zohreh Hojati, +5 authors, Mazdak Ganjalikhani-Hakemi.
Front Oncol, 2021 Jun 01; 11. PMID: 34055618    Free PMC article.
Regulatory T Cells: Barriers of Immune Infiltration Into the Tumor Microenvironment.
Ellen N Scott, Angela M Gocher, Creg J Workman, Dario A A Vignali.
Front Immunol, 2021 Jun 29; 12. PMID: 34177968    Free PMC article.
Review.