Research Article

Recent Advances on T Regulatory Cells

Authors

  • Balid Albarbar Lecturer in Immunology, Department of Medical Laboratory, Higher Institute of Sciences & Medical Technology, Libya

Abstract

Active suppression of tumour-reactive T cells can limit both immune surveillance and immunotherapy. Development of cancer results into the generation of immune suppressive network to inhibit anti-tumour activity and evade the host’s immune response, which eventually facilitates tumour progression. Emerging evidence indicates that immunosuppressive cells; T regulatory cells (Tregs) may be largely responsible for inhibiting host T-cell activity against tumour-associated antigens and impair the effectiveness of anticancer immunotherapeutic approaches. Reducing the deleterious effects of Treg may increase the success of various immunotherapeutic modalities in cancer. However, an increase in our understanding of the local tumour microenvironment and the exact mechanisms of Treg induction and/or expansion in peripheral blood and tumour microenvironment of cancer patients should provide opportunities to test different treatments to target these immunosuppressive cells and alter the balance in favor of generating effective anti-tumour immune responses. The purpose of this study is to provide information about the phenotype, role and the function of Tregs and the mechanisms of their expansion in cancer.

Article information

Journal

International Journal of Biological, Physical and Chemical Studies

Volume (Issue)

1 (1)

Pages

30-38

Published

2019-12-30

How to Cite

Albarbar, B. (2019). Recent Advances on T Regulatory Cells. International Journal of Biological, Physical and Chemical Studies , 1(1), 30-38. https://al-kindipublisher.com/index.php/ijbpcs/article/view/424

References

Akasaki, Y., Liu, G., Chung, N. H., Ehtesham, M., Black, K. L., & John, S. Y. (2004). Induction of a CD4+ T regulatory type 1 response by cyclooxygenase-2-overexpressing glioma. The Journal of Immunology, 173(7), 4352-4359.

Alsaab, H. O., Sau, S., Alzhrani, R., Tatiparti, K., Bhise, K., Kashaw, S. K., & Iyer, A. K. (2017). PD-1 and PD-L1 checkpoint signaling inhibition for cancer immunotherapy: mechanism, combinations, and clinical outcome. Frontiers in pharmacology, 8, 561.

Andersen, M. H., Sørensen, R. B., Brimnes, M. K., Svane, I. M., Becker, J. C., & thor Straten, P. (2009). Identification of heme oxygenase-1–specific regulatory CD8+ T cells in cancer patients. The Journal of clinical investigation, 119(8), 2245-2256.

Anderson, A. C., Joller, N., & Kuchroo, V. K. (2016). Lag-3, Tim-3, and TIGIT: co-inhibitory receptors with specialized functions in immune regulation. Immunity, 44(5), 989-1004.

Bailur, J. K., Gueckel, B., Derhovanessian, E., & Pawelec, G. (2015). Presence of circulating Her2-reactive CD8+ T-cells is associated with lower frequencies of myeloid-derived suppressor cells and regulatory T cells, and better survival in older breast cancer patients. Breast Cancer Research, 17(1), 34.

Bergmann, C., Strauss, L., Zeidler, R., Lang, S., & Whiteside, T. L. (2007). Expansion of human T regulatory type 1 cells in the microenvironment of cyclooxygenase 2 overexpressing head and neck squamous cell carcinoma. Cancer research, 67(18), 8865-8873.

Bluestone, J. A., & Abbas, A. K. (2003). Natural versus adaptive regulatory T cells. Nature Reviews Immunology, 3(3), 253-257.

Bu, X., Mahoney, K. M., & Freeman, G. J. (2016). Learning from PD-1 resistance: new combination strategies. Trends in molecular medicine, 22(6), 448-451.

Cekic, C., & Linden, J. (2016). Purinergic regulation of the immune system. Nature Reviews Immunology, 16(3), 177.

Chaput, N., Louafi, S., Bardier, A., Charlotte, F., Vaillant, J.-C., Ménégaux, F., . . . Taieb, J. (2009). Identification of CD8+ CD25+ Foxp3+ suppressive T cells in colorectal cancer tissue. Gut, 58(4), 520-529.

Chaudhary, B., & Elkord, E. (2016). Regulatory T cells in the tumor microenvironment and cancer progression: role and therapeutic targeting. Vaccines, 4(3), 28.

Chen, M.-L., Yan, B.-S., Bando, Y., Kuchroo, V. K., & Weiner, H. L. (2008). Latency-associated peptide identifies a novel CD4+ CD25+ regulatory T cell subset with TGFβ-mediated function and enhanced suppression of experimental autoimmune encephalomyelitis. The Journal of Immunology, 180(11), 7327-7337.

Chen, W., Jin, W., Hardegen, N., Lei, K.-j., Li, L., Marinos, N., . . . Wahl, S. M. (2003). Conversion of peripheral CD4+ CD25− naive T cells to CD4+ CD25+ regulatory T cells by TGF-β induction of transcription factor Foxp3. The Journal of experimental medicine, 198(12), 1875-1886.

Collison, L. W., Chaturvedi, V., Henderson, A. L., Giacomin, P. R., Guy, C., Bankoti, J., . . . Brown, S. A. (2010). IL-35-mediated induction of a potent regulatory T cell population. Nature immunology, 11(12), 1093.

Curiel, T. J. (2008). Regulatory T cells and treatment of cancer. Current opinion in immunology, 20(2), 241-246.

Dannull, J., Su, Z., Rizzieri, D., Yang, B. K., Coleman, D., Yancey, D., . . . Gilboa, E. (2005). Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells. The Journal of clinical investigation, 115(12), 3623-3633.

de Lafaille, M. A. C., & Lafaille, J. J. (2009). Natural and adaptive foxp3+ regulatory T cells: more of the same or a division of labor? Immunity, 30(5), 626-635.

Deaglio, S., Dwyer, K. M., Gao, W., Friedman, D., Usheva, A., Erat, A., . . . Oukka, M. (2007). Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. The Journal of experimental medicine, 204(6), 1257-1265.

Demaria, S. (2013). Immune escape: immunosuppressive networks Cancer Immunotherapy (pp. 149-164): Elsevier.

Dhuban, K. B., d’Hennezel, E., Nashi, E., Bar-Or, A., Rieder, S., Shevach, E. M., . . . Piccirillo, C. A. (2015). Coexpression of TIGIT and FCRL3 identifies Helios+ human memory regulatory T cells. The Journal of Immunology, 194(8), 3687-3696.

Dijke, I., Hoeppli, R., Ellis, T., Pearcey, J., Huang, Q., McMurchy, A., . . . Larsen, I. (2016). Discarded human thymus is a novel source of stable and long‐lived therapeutic regulatory T cells. American Journal of Transplantation, 16(1), 58-71.

Dunn, G. P., Bruce, A. T., Ikeda, H., Old, L. J., & Schreiber, R. D. (2002). Cancer immunoediting: from immunosurveillance to tumor escape. Nature immunology, 3(11), 991-998.

Eggermont, A. M., Chiarion-Sileni, V., Grob, J.-J., Dummer, R., Wolchok, J. D., Schmidt, H., . . . Richards, J. M. (2016). Prolonged survival in stage III melanoma with ipilimumab adjuvant therapy. New England Journal of Medicine, 375(19), 1845-1855.

Filaci, G., Fenoglio, D., Fravega, M., Ansaldo, G., Borgonovo, G., Traverso, P., . . . Rizzi, M. (2007). CD8+ CD28− T regulatory lymphocytes inhibiting T cell proliferative and cytotoxic functions infiltrate human cancers. The Journal of Immunology, 179(7), 4323-4334.

Filippi, C. M., Juedes, A. E., Oldham, J. E., Ling, E., Togher, L., Peng, Y., . . . von Herrath, M. G. (2008). Transforming growth factor-β suppresses the activation of CD8+ T-cells when naive but promotes their survival and function once antigen experienced: a two-faced impact on autoimmunity. Diabetes, 57(10), 2684-2692.

Fontenot, J. D., Gavin, M. A., & Rudensky, A. Y. (2003). Foxp3 programs the development and function of CD4+ CD25+ regulatory T cells. Nature immunology, 4(4), 330-336.

Francisco, L. M., Salinas, V. H., Brown, K. E., Vanguri, V. K., Freeman, G. J., Kuchroo, V. K., & Sharpe, A. H. (2009). PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. Journal of Experimental Medicine, 206(13), 3015-3029.

Fu, W., Ergun, A., Lu, T., Hill, J. A., Haxhinasto, S., Fassett, M. S., . . . Chan, S. (2012). A multiply redundant genetic switch'locks in'the transcriptional signature of regulatory T cells. Nature immunology, 13(10), 972.

Gallimore, A. M., & Simon, A. (2008). Positive and negative influences of regulatory T cells on tumour immunity. Oncogene, 27(45), 5886-5893.

Gobert, M., Treilleux, I., Bendriss-Vermare, N., Bachelot, T., Goddard-Leon, S., Arfi, V., . . . Olive, D. (2009). Regulatory T cells recruited through CCL22/CCR4 are selectively activated in lymphoid infiltrates surrounding primary breast tumors and lead to an adverse clinical outcome. Cancer research, 69(5), 2000-2009.

Gomella, L. G., Sargent, E. R., Linehan, W. M., & Kasid, A. (1989). Transforming growth factor-beta inhibits the growth of renal cell carcinoma in vitro. The Journal of urology, 141(5), 1240-1244.

Grazia Roncarolo, M., Gregori, S., Battaglia, M., Bacchetta, R., Fleischhauer, K., & Levings, M. K. (2006). Interleukin‐10‐secreting type 1 regulatory T cells in rodents and humans. Immunological reviews, 212(1), 28-50.

Gruenbacher, G., Gander, H., Rahm, A., Idzko, M., Nussbaumer, O., & Thurnher, M. (2016). Ecto-ATPase CD39 inactivates isoprenoid-derived Vγ9Vδ2 T cell phosphoantigens. Cell reports, 16(2), 444-456.

Guo, Z., Jang, M. H., Otani, K., Bai, Z., Umemoto, E., Matsumoto, M., . . . Matsushima, K. (2008). CD4+ CD25+ regulatory T cells in the small intestinal lamina propria show an effector/memory phenotype. International immunology, 20(3), 307-315.

Gupta, S., & Agrawal, S. (2020). In vitro Effects of CD8+ Regulatory T Cells on Human B Cell Subpopulations. International Archives of Allergy and Immunology, 1-5.

Ha, S.-J., Park, H. J., Park, J. S., Jeong, Y. H., Son, J., Ban, Y. H., . . . Chung, D. H. (2016). Role of PD-1 in regulatory T cells during chronic virus infection: Am Assoc Immnol.

Hawrylowicz, C., & O'garra, A. (2005). Potential role of interleukin-10-secreting regulatory T cells in allergy and asthma. Nature Reviews Immunology, 5(4), 271-283.

Himmel, M. E., MacDonald, K. G., Garcia, R. V., Steiner, T. S., & Levings, M. K. (2013). Helios+ and Helios− cells coexist within the natural FOXP3+ T regulatory cell subset in humans. The Journal of Immunology, 190(5), 2001-2008.

Hirahara, K., Liu, L., Clark, R. A., Yamanaka, K.-i., Fuhlbrigge, R. C., & Kupper, T. S. (2006). The majority of human peripheral blood CD4+ CD25highFoxp3+ regulatory T cells bear functional skin-homing receptors. The Journal of Immunology, 177(7), 4488-4494.

Hodi, F. S., Chesney, J., Pavlick, A. C., Robert, C., Grossmann, K. F., McDermott, D. F., . . . Agarwala, S. S. (2016). Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial. The Lancet Oncology, 17(11), 1558-1568.

Holderried, T. A., Lang, P. A., Kim, H.-J., & Cantor, H. (2013). Genetic disruption of CD8+ Treg activity enhances the immune response to viral infection. Proceedings of the National Academy of Sciences, 110(52), 21089-21094.

Holt, M. P., Punkosdy, G. A., Glass, D. D., & Shevach, E. M. (2017). TCR signaling and CD28/CTLA-4 signaling cooperatively modulate T regulatory cell homeostasis. The Journal of Immunology, 198(4), 1503-1511.

Hori, S., Nomura, T., & Sakaguchi, S. (2003). Control of regulatory T cell development by the transcription factor Foxp3. Science, 299(5609), 1057-1061.

Huard, B., Prigent, P., Tournier, M., Bruniquel, D., & Triebel, F. (1995). CD4/major histocompatibility complex class II interaction analyzed with CD4‐and lymphocyte activation gene‐3 (LAG‐3)‐Ig fusion proteins. European journal of immunology, 25(9), 2718-2721.

Inobe, J. i., Slavin, A. J., Komagata, Y., Chen, Y., Liu, L., & Weiner, H. L. (1998). IL‐4 is a differentiation factor for transforming growth factor‐β secreting Th3 cells and oral administration of IL‐4 enhances oral tolerance in experimental allergic encephalomyelitis. European journal of immunology, 28(9), 2780-2790.

Jacobs, J. F., Idema, A. J., Bol, K. F., Grotenhuis, J. A., de Vries, I. J. M., Wesseling, P., & Adema, G. J. (2010). Prognostic significance and mechanism of Treg infiltration in human brain tumors. Journal of neuroimmunology, 225(1-2), 195-199.

Jeron, A., Pfoertner, S., Bruder, D., Geffers, R., Hammerer, P., Hofmann, R., . . . Schrader, A. J. (2009). Frequency and gene expression profile of regulatory T cells in renal cell carcinoma. Tumor Biology, 30(3), 160-170.

Jiang, S., Tugulea, S., Pennesi, G., Liu, Z., Mulder, A., Lederman, S., . . . Suciu-Foca, N. (1998). Induction of MHC-class I restricted human suppressor T cells by peptide priming in vitro. Human immunology, 59(11), 690-699.

Joller, N., Lozano, E., Burkett, P. R., Patel, B., Xiao, S., Zhu, C., . . . Yajnik, V. (2014). Treg cells expressing the coinhibitory molecule TIGIT selectively inhibit proinflammatory Th1 and Th17 cell responses. Immunity, 40(4), 569-581.

Keir, M. E., Butte, M. J., Freeman, G. J., & Sharpe, A. H. (2008). PD-1 and its ligands in tolerance and immunity. Annu. Rev. Immunol., 26, 677-704.

Kim, B.-S., Nishikii, H., Baker, J., Pierini, A., Schneidawind, D., Pan, Y., . . . Negrin, R. S. (2015). Treatment with agonistic DR3 antibody results in expansion of donor Tregs and reduced graft-versus-host disease. Blood, The Journal of the American Society of Hematology, 126(4), 546-557.

Kim, H.-J., Barnitz, R. A., Kreslavsky, T., Brown, F. D., Moffett, H., Lemieux, M. E., . . . Chan, S. (2015). Stable inhibitory activity of regulatory T cells requires the transcription factor Helios. Science, 350(6258), 334-339.

Kim, H.-J., Verbinnen, B., Tang, X., Lu, L., & Cantor, H. (2010). Inhibition of follicular T-helper cells by CD8+ regulatory T cells is essential for self tolerance. Nature, 467(7313), 328-332.

Kim, Y. C., Bhairavabhotla, R., Yoon, J., Golding, A., Thornton, A. M., Tran, D. Q., & Shevach, E. M. (2012). Oligodeoxynucleotides stabilize Helios-expressing Foxp3+ human T regulatory cells during in vitro expansion. Blood, The Journal of the American Society of Hematology, 119(12), 2810-2818.

Klarquist, J., Tobin, K., Oskuei, P. F., Henning, S. W., Fernandez, M. F., Dellacecca, E. R., . . . Mehrotra, S. (2016). Ccl22 diverts T regulatory cells and controls the growth of melanoma. Cancer research, 76(21), 6230-6240.

Kleinewietfeld, M., Puentes, F., Borsellino, G., Battistini, L., Rötzschke, O., & Falk, K. (2005). CCR6 expression defines regulatory effector/memory-like cells within the CD25+ CD4+ T-cell subset. Blood, 105(7), 2877-2886.

Klocke, K., Holmdahl, R., & Wing, K. (2017). CTLA‐4 expressed by FOXP3+ regulatory T cells prevents inflammatory tissue attack and not T‐cell priming in arthritis. Immunology, 152(1), 125-137.

Kurtulus, S., Sakuishi, K., Ngiow, S.-F., Joller, N., Tan, D. J., Teng, M. W., . . . Anderson, A. C. (2015). TIGIT predominantly regulates the immune response via regulatory T cells. The Journal of clinical investigation, 125(11), 4053-4062.

Leonard, J. D., Gilmore, D. C., Dileepan, T., Nawrocka, W. I., Chao, J. L., Schoenbach, M. H., . . . Savage, P. A. (2017). Identification of natural regulatory T cell epitopes reveals convergence on a dominant autoantigen. Immunity, 47(1), 107-117. e108.

Li, X., & Zheng, Y. (2015). Regulatory T cell identity: formation and maintenance. Trends in immunology, 36(6), 344-353.

Lin, X., Chen, M., Liu, Y., Guo, Z., He, X., Brand, D., & Zheng, S. G. (2013). Advances in distinguishing natural from induced Foxp3+ regulatory T cells. International journal of clinical and experimental pathology, 6(2), 116.

Lozano, E., Dominguez-Villar, M., Kuchroo, V., & Hafler, D. A. (2012). The TIGIT/CD226 axis regulates human T cell function. The Journal of Immunology, 188(8), 3869-3875.

Madireddi, S., Eun, S.-Y., Mehta, A. K., Birta, A., Zajonc, D. M., Niki, T., . . . Croft, M. (2017). Regulatory T Cell–Mediated Suppression of Inflammation Induced by DR3 Signaling Is Dependent on Galectin-9. The Journal of Immunology, 199(8), 2721-2728.

Manieri, N. A., Chiang, E. Y., & Grogan, J. L. (2017). TIGIT: a key inhibitor of the cancer immunity cycle. Trends in immunology, 38(1), 20-28.

Mohr, A., Malhotra, R., Mayer, G., Gorochov, G., & Miyara, M. (2018). Human FOXP 3+ T regulatory cell heterogeneity. Clinical & Translational Immunology, 7(1), e1005.

Nishikawa, H., & Sakaguchi, S. (2010). Regulatory T cells in tumor immunity. International journal of cancer, 127(4), 759-767.

Nishimura, H., & Honjo, T. (2001). PD-1: an inhibitory immunoreceptor involved in peripheral tolerance. Trends in immunology, 22(5), 265-268.

Noyan, F., Lee, Y. S., Zimmermann, K., Hardtke‐Wolenski, M., Taubert, R., Warnecke, G., . . . Manns, M. P. (2014). Isolation of human antigen‐specific regulatory T cells with high suppressive function. European journal of immunology, 44(9), 2592-2602.

Peggs, K. S., Quezada, S. A., Chambers, C. A., Korman, A. J., & Allison, J. P. (2009). Blockade of CTLA-4 on both effector and regulatory T cell compartments contributes to the antitumor activity of anti–CTLA-4 antibodies. Journal of Experimental Medicine, 206(8), 1717-1725.

Postow, M. A., Chesney, J., Pavlick, A. C., Robert, C., Grossmann, K., McDermott, D., . . . Agarwala, S. S. (2015). Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. New England Journal of Medicine, 372(21), 2006-2017.

Povoleri, G. A. M., Scottà, C., Nova-Lamperti, E. A., John, S., Lombardi, G., & Afzali, B. (2013). Thymic versus induced regulatory T cells–who regulates the regulators? Frontiers in immunology, 4, 169.

Preston, C. C., Maurer, M. J., Oberg, A. L., Visscher, D. W., Kalli, K. R., Hartmann, L. C., . . . Knutson, K. L. (2013). The ratios of CD8+ T cells to CD4+ CD25+ FOXP3+ and FOXP3-T cells correlate with poor clinical outcome in human serous ovarian cancer. PloS one, 8(11).

Robert, C., Ribas, A., Schachter, J., Arance, A., Grob, J.-J., Mortier, L., . . . Lotem, M. (2019). Pembrolizumab versus ipilimumab in advanced melanoma (KEYNOTE-006): post-hoc 5-year results from an open-label, multicentre, randomised, controlled, phase 3 study. The Lancet Oncology, 20(9), 1239-1251.

Robert, C., Schachter, J., Long, G. V., Arance, A., Grob, J. J., Mortier, L., . . . Lotem, M. (2015). Pembrolizumab versus ipilimumab in advanced melanoma. New England Journal of Medicine, 372(26), 2521-2532.

Routy, B., Le Chatelier, E., Derosa, L., Duong, C. P., Alou, M. T., Daillère, R., . . . Roberti, M. P. (2018). Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors. Science, 359(6371), 91-97.

Rudensky, A. Y. (2011). Regulatory T cells and Foxp3. Immunological reviews, 241(1), 260-268.

Sakaguchi, S., Sakaguchi, N., Asano, M., Itoh, M., & Toda, M. (1995). Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. The Journal of Immunology, 155(3), 1151-1164.

Samy, E. T., Parker, L. A., Sharp, C. P., & Tung, K. S. (2005). Continuous control of autoimmune disease by antigen-dependent polyclonal CD4+ CD25+ regulatory T cells in the regional lymph node. The Journal of experimental medicine, 202(6), 771-781.

Santodomingo‐Garzon, T., Han, J., Le, T., Yang, Y., & Swain, M. G. (2009). Natural killer T cells regulate the homing of chemokine CXC receptor 3‐positive regulatory T cells to the liver in mice. Hepatology, 49(4), 1267-1276.

Schallenberg, S., Tsai, P.-Y., Riewaldt, J., & Kretschmer, K. (2010). Identification of an immediate Foxp3− precursor to Foxp3+ regulatory T cells in peripheral lymphoid organs of nonmanipulated mice. Journal of Experimental Medicine, 207(7), 1393-1407.

Schmidt, A., Oberle, N., & Krammer, P. H. (2012). Molecular mechanisms of treg-mediated T cell suppression. Frontiers in immunology, 3, 51.

Schmidt, E. M., Wang, C. J., Ryan, G. A., Clough, L. E., Qureshi, O. S., Goodall, M., . . . Walker, L. S. (2009). Ctla-4 controls regulatory T cell peripheral homeostasis and is required for suppression of pancreatic islet autoimmunity. The Journal of Immunology, 182(1), 274-282.

Schoenbrunn, A., Frentsch, M., Kohler, S., Keye, J., Dooms, H., Moewes, B., . . . Wu, P. (2012). A converse 4-1BB and CD40 ligand expression pattern delineates activated regulatory T cells (Treg) and conventional T cells enabling direct isolation of alloantigen-reactive natural Foxp3+ Treg. The Journal of Immunology, 189(12), 5985-5994.

Sebastian, M., Lopez-Ocasio, M., Metidji, A., Rieder, S. A., Shevach, E. M., & Thornton, A. M. (2016). Helios controls a limited subset of regulatory T cell functions. The Journal of Immunology, 196(1), 144-155.

Sharma, M. D., Huang, L., Choi, J.-H., Lee, E.-J., Wilson, J. M., Lemos, H., . . . Mellor, A. L. (2013). An inherently bifunctional subset of Foxp3+ T helper cells is controlled by the transcription factor eos. Immunity, 38(5), 998-1012.

Shevach, E. M. (2009). Mechanisms of foxp3+ T regulatory cell-mediated suppression. Immunity, 30(5), 636-645.

Smyth, G. P., Stapleton, P. P., Barden, C. B., Mestre, J. R., Freeman, T. A., Duff, M. D., . . . Daly, J. M. (2003). Renal cell carcinoma induces prostaglandin E 2 and T-helper type 2 cytokine production in peripheral blood mononuclear cells. Annals of surgical oncology, 10(4), 455-462.

Sugita, K., Hanakawa, S., Honda, T., Kondoh, G., Miyachi, Y., Kabashima, K., & Nomura, T. (2015). Generation of Helios reporter mice and an evaluation of the suppressive capacity of Helios+ regulatory T cells in vitro. Experimental dermatology, 24(7), 554-556.

Sun, L., Jin, H., & Li, H. (2016). GARP: a surface molecule of regulatory T cells that is involved in the regulatory function and TGF-β releasing. Oncotarget, 7(27), 42826.

Talmadge, J. E. (2007). Pathways mediating the expansion and immunosuppressive activity of myeloid-derived suppressor cells and their relevance to cancer therapy. Clinical Cancer Research, 13(18), 5243-5248.

Tang, A. L., Teijaro, J. R., Njau, M. N., Chandran, S. S., Azimzadeh, A., Nadler, S. G., . . . Farber, D. L. (2008). CTLA4 expression is an indicator and regulator of steady-state CD4+ FoxP3+ T cell homeostasis. The Journal of Immunology, 181(3), 1806-1813.

Tang, Q., & Bluestone, J. A. (2008). The Foxp3+ regulatory T cell: a jack of all trades, master of regulation. Nature immunology, 9(3), 239-244.

Tatsumi, T., Herrem, C. J., Olson, W. C., Finke, J. H., Bukowski, R. M., Kinch, M. S., . . . Storkus, W. J. (2003). Disease stage variation in CD4+ and CD8+ T-cell reactivity to the receptor tyrosine kinase EphA2 in patients with renal cell carcinoma. Cancer research, 63(15), 4481-4489.

Thornton, A. M., Korty, P. E., Tran, D. Q., Wohlfert, E. A., Murray, P. E., Belkaid, Y., & Shevach, E. M. (2010). Expression of Helios, an Ikaros transcription factor family member, differentiates thymic-derived from peripherally induced Foxp3+ T regulatory cells. The Journal of Immunology, 184(7), 3433-3441.

Tran, D. Q., Andersson, J., Hardwick, D., Bebris, L., Illei, G. G., & Shevach, E. M. (2009). Selective expression of latency-associated peptide (LAP) and IL-1 receptor type I/II (CD121a/CD121b) on activated human FOXP3+ regulatory T cells allows for their purification from expansion cultures. Blood, The Journal of the American Society of Hematology, 113(21), 5125-5133.

Tran, D. Q., Andersson, J., Wang, R., Ramsey, H., Unutmaz, D., & Shevach, E. M. (2009). GARP (LRRC32) is essential for the surface expression of latent TGF-β on platelets and activated FOXP3+ regulatory T cells. Proceedings of the National Academy of Sciences, 106(32), 13445-13450.

Wada, J., Suzuki, H., Fuchino, R., Yamasaki, A., Nagai, S., Yanai, K., . . . Morisaki, T. (2009). The contribution of vascular endothelial growth factor to the induction of regulatory T-cells in malignant effusions. Anticancer research, 29(3), 881-888.

Wang, H. Y., Lee, D. A., Peng, G., Guo, Z., Li, Y., Kiniwa, Y., . . . Wang, R.-F. (2004). Tumor-specific human CD4+ regulatory T cells and their ligands: implications for immunotherapy. Immunity, 20(1), 107-118.

Wang, H. Y., Peng, G., Guo, Z., Shevach, E. M., & Wang, R.-F. (2005). Recognition of a new ARTC1 peptide ligand uniquely expressed in tumor cells by antigen-specific CD4+ regulatory T cells. The Journal of Immunology, 174(5), 2661-2670.

Wang, H. Y., & Wang, R.-F. (2007). Regulatory T cells and cancer. Current opinion in immunology, 19(2), 217-223.

Weiner, H. L. (2001). Induction and mechanism of action of transforming growth factor‐β‐secreting Th3 regulatory cells. Immunological reviews, 182(1), 207-214.

Weiss, J. M., Bilate, A. M., Gobert, M., Ding, Y., Curotto de Lafaille, M. A., Parkhurst, C. N., . . . Ruocco, M. G. (2012). Neuropilin 1 is expressed on thymus-derived natural regulatory T cells, but not mucosa-generated induced Foxp3+ T reg cells. Journal of Experimental Medicine, 209(10), 1723-1742.

Whiteside, T. L. (2015). The role of regulatory T cells in cancer immunology. ImmunoTargets and therapy, 4, 159.

Wing, K., Yamaguchi, T., & Sakaguchi, S. (2011). Cell-autonomous and-non-autonomous roles of CTLA-4 in immune regulation. Trends in immunology, 32(9), 428-433.

Woo, E. Y., Chu, C. S., Goletz, T. J., Schlienger, K., Yeh, H., Coukos, G., . . . June, C. H. (2001). Regulatory CD4+ CD25+ T cells in tumors from patients with early-stage non-small cell lung cancer and late-stage ovarian cancer. Cancer research, 61(12), 4766-4772.

Woods, D. M., Ramakrishnan, R., Sodré, A. L., Berglund, A., & Weber, J. (2017). PD-1 blockade induces phosphorylated STAT3 and results in an increase of Tregs with reduced suppressive function: Am Assoc Immnol.

Yadav, M., Louvet, C., Davini, D., Gardner, J. M., Martinez-Llordella, M., Bailey-Bucktrout, S., . . . Kuster, D. J. (2012). Neuropilin-1 distinguishes natural and inducible regulatory T cells among regulatory T cell subsets in vivo. Journal of Experimental Medicine, 209(10), 1713-1722.

Yamaguchi, T., Wing, J. B., & Sakaguchi, S. (2011). Two modes of immune suppression by Foxp3+ regulatory T cells under inflammatory or non-inflammatory conditions. Paper presented at the Seminars in immunology.

Yamamoto, T., Yanagimoto, H., Satoi, S., Toyokawa, H., Hirooka, S., Yamaki, S., . . . Kwon, A.-H. (2012). Circulating CD4+ CD25+ regulatory T cells in patients with pancreatic cancer. Pancreas, 41(3), 409-415.

Yamazaki, T., Yang, X. O., Chung, Y., Fukunaga, A., Nurieva, R., Pappu, B., . . . Panopoulos, A. D. (2008). CCR6 regulates the migration of inflammatory and regulatory T cells. The Journal of Immunology, 181(12), 8391-8401.

Zhao, H., Liao, X., & Kang, Y. (2017). Tregs: where we are and what comes next? Frontiers in immunology, 8, 1578.

Zhou, W., Deng, J., Chen, Q., Li, R., Xu, X., Guan, Y., . . . Li, J. (2020). Expression of CD4+ CD25+ CD127Low regulatory T cells and cytokines in peripheral blood of patients with primary liver carcinoma. International Journal of Medical Sciences, 17(6), 712.

Downloads

Views

63

Downloads

36

Keywords:

T regulatory cells (Tregs), Myeloid derived suppressor cells (MDSCs), antigen presenting cells (APCs), dendritic cells (DCs), forkhead box P3 (FoxP3 ), natural Tregs (nTregs) and induced Tregs (iTregs).