138
Views
21
CrossRef citations to date
0
Altmetric
Review

Mechanisms of T-cell inhibition: implications for cancer immunotherapy

&
Pages 89-105 | Published online: 09 Jan 2014

References

  • Van Pel A, Boon T. Protection against a nonimmunogenic mouse leukemia by an immunogenic variant obtained by mutagenesis. Proc. Natl Acad. Sci. USA79(15), 4718–4722 (1982).
  • van der Bruggen P, Traversari C, Chomez P et al. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science254(5038), 1643–1647 (1991).
  • Clark WH Jr, Elder DE, Guerry Dt et al. Model predicting survival in stage I melanoma based on tumor progression. J. Natl Cancer Inst.81(24), 1893–1904 (1989).
  • Clemente CG, Mihm MC Jr, Bufalino R et al. Prognostic value of tumor infiltrating lymphocytes in the vertical growth phase of primary cutaneous melanoma. Cancer77(7), 1303–1310 (1996).
  • Mihm MC Jr, Clemente CG, Cascinelli N. Tumor infiltrating lymphocytes in lymph node melanoma metastases: a histopathologic prognostic indicator and an expression of local immune response. Lab. Invest.74(1), 43–47 (1996).
  • Baxevanis CN, Dedoussis GV, Papadopoulos NG et al. Tumor specific cytolysis by tumor infiltrating lymphocytes in breast cancer. Cancer74(4), 1275–1282 (1994).
  • Marrogi AJ, Munshi A, Merogi AJ et al. Study of tumor infiltrating lymphocytes and transforming growth factor-β as prognostic factors in breast carcinoma. Int. J. Cancer74(5), 492–501 (1997).
  • Naito Y, Saito K, Shiiba K et al. CD8+ T cells infiltrated within cancer cell nests as a prognostic factor in human colorectal cancer. Cancer Res.58(16), 3491–3494 (1998).
  • Pages F, Berger A, Camus M et al. Effector memory T cells, early metastasis, and survival in colorectal cancer. N. Engl. J. Med.353(25), 2654–2666 (2005).
  • Schumacher K, Haensch W, Roefzaad C, Schlag PM. Prognostic significance of activated CD8(+) T cell infiltrations within esophageal carcinomas. Cancer Res.61(10), 3932–3936 (2001).
  • Zhang L, Conejo-Garcia JR, Katsaros D et al. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N. Engl. J. Med.348(3), 203–213 (2003).
  • Vesalainen S, Lipponen P, Talja M, Syrjanen K. Histological grade, perineural infiltration, tumour-infiltrating lymphocytes and apoptosis as determinants of long-term prognosis in prostatic adenocarcinoma. Eur. J. Cancer30A(12), 1797–1803 (1994).
  • Sharma P, Shen Y, Wen S et al. CD8 tumor-infiltrating lymphocytes are predictive of survival in muscle-invasive urothelial carcinoma. Proc. Natl Acad. Sci. USA104(10), 3967–3972 (2007).
  • Nakano O, Sato M, Naito Y et al. Proliferative activity of intratumoral CD8(+) T-lymphocytes as a prognostic factor in human renal cell carcinoma: clinicopathologic demonstration of antitumor immunity. Cancer Res.61(13), 5132–5136 (2001).
  • Rosenberg SA, Sherry RM, Morton KE et al. Tumor progression can occur despite the induction of very high levels of self/tumor antigen-specific CD8+ T cells in patients with melanoma. J. Immunol.175(9), 6169–6176 (2005).
  • Quezada SA, Peggs KS, Simpson TR et al. Limited tumor infiltration by activated T effector cells restricts the therapeutic activity of regulatory T cell depletion against established melanoma. J. Exp. Med.205(9), 2125–2138 (2008).
  • Whiteside TL. The tumor microenvironment and its role in promoting tumor growth. Oncogene27(45), 5904–5912 (2008).
  • Schwartz RH. T cell anergy. Annu. Rev. Immunol.21, 305–334 (2003).
  • Camponi M, Chang C, Ferrone S. HLA class I antigen loss, tumor immune escape and immune selection. Vaccine20(Suppl. 4), A40–A45 (2002).
  • Chen W, Jin W, Hardegen N et al. Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-β induction of transcription factor Foxp3. J. Exp. Med.198(12), 1875–1886 (2003).
  • Gabrilovich DI, Ishida T, Nadaf S, Ohm JE, Carbone DP. Antibodies to vascular endothelial growth factor enhance the efficacy of cancer immunotherapy by improving endogenous dendritic cell function. Clin. Cancer Res.5(10), 2963–2970 (1999).
  • Gorelik L, Flavell RA. Immune-mediated eradication of tumors through the blockade of transforming growth factor-β signaling in T cells. Nat. Med.7(10), 1118–1122 (2001).
  • Kawamura K, Bahar R, Natsume W, Sakiyama S, Tagawa M. Secretion of interleukin-10 from murine colon carcinoma cells suppresses systemic antitumor immunity and impairs protective immunity induced against the tumors. Cancer Gene Ther.9(1), 109–115 (2002).
  • McKallip R, Li R, Ladisch S. Tumor gangliosides inhibit the tumor-specific immune response. J. Immunol.163(7), 3718–3726 (1999).
  • Mellor AL, Munn DH. Creating immune privilege: active local suppression that benefits friends, but protects foes. Nat. Rev. Immunol.8(1), 74–80 (2008).
  • Munn DH, Mellor AL. Indoleamine 2,3-dioxygenase and tumor-induced tolerance. J. Clin. Invest.117(5), 1147–1154 (2007).
  • Korman AJ, Peggs KS, Allison JP. Checkpoint blockade in cancer immunotherapy. Adv. Immunol.90, 297–339 (2006).
  • Peggs KS, Quezada SA, Allison JP. Cell intrinsic mechanisms of T-cell inhibition and application to cancer therapy. Immunol. Rev.224, 141–165 (2008).
  • Butte MJ, Keir ME, Phamduy TB, Sharpe AH, Freeman GJ. Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses. Immunity27(1), 111–122 (2007).
  • Mueller DL, Jenkins MK, Schwartz RH. Clonal expansion versus functional clonal inactivation: a costimulatory signalling pathway determines the outcome of T cell antigen receptor occupancy. Annu. Rev. Immunol.7, 445–480 (1989).
  • Harding FA, McArthur JG, Gross JA, Raulet DH, Allison JP. CD28-mediated signalling co-stimulates murine T cells and prevents induction of anergy in T-cell clones. Nature356(6370), 607–609 (1992).
  • Lenschow DJ, Bluestone JA. T cell co-stimulation and in vivo tolerance. Curr. Opin. Immunol.5(5), 747–752 (1993).
  • Kundig TM, Shahinian A, Kawai K et al. Duration of TCR stimulation determines costimulatory requirement of T cells. Immunity5(1), 41–52 (1996).
  • Shahinian A, Pfeffer K, Lee KP et al. Differential T cell costimulatory requirements in CD28-deficient mice. Science261(5121), 609–612 (1993).
  • Brunet JF, Denizot F, Luciani MF et al. A new member of the immunoglobulin superfamily – CTLA-4. Nature328(6127), 267–270 (1987).
  • Dariavach P, Mattei MG, Golstein P, Lefranc MP. Human Ig superfamily CTLA-4 gene: chromosomal localization and identity of protein sequence between murine and human CTLA-4 cytoplasmic domains. Eur J. Immunol.18(12), 1901–1905 (1988).
  • Linsley PS, Brady W, Grosmaire L et al. Binding of the B cell activation antigen B7 to CD28 costimulates T cell proliferation and interleukin 2 mRNA accumulation. J. Exp. Med.173(3), 721–730 (1991).
  • Linsley PS, Brady W, Urnes M et al. CTLA-4 is a second receptor for the B cell activation antigen B7. J. Exp. Med.174(3), 561–569 (1991).
  • Krummel MF, Allison JP. CTLA-4 engagement inhibits IL-2 accumulation and cell cycle progression upon activation of resting T cells. J. Exp. Med.183(6), 2533–2540 (1996).
  • Krummel MF, Allison JP. CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation. J. Exp. Med.182(2), 459–465 (1995).
  • Chambers CA, Sullivan TJ, Allison JP. Lymphoproliferation in CTLA-4-deficient mice is mediated by costimulation-dependent activation of CD4+ T cells. Immunity7(6), 885–895 (1997).
  • Tivol EA, Borriello F, Schweitzer AN et al. Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity3(5), 541–547 (1995).
  • Waterhouse P, Penninger JM, Timms E et al. Lymphoproliferative disorders with early lethality in mice deficient in CTLA-4. Science270(5238), 985–988 (1995).
  • Iida T, Ohno H, Nakaseko C et al. Regulation of cell surface expression of CTLA-4 by secretion of CTLA-4-containing lysosomes upon activation of CD4+ T cells. J. Immunol.165(9), 5062–5068 (2000).
  • Walunas TL, Lenschow DJ, Bakker CY et al. CTLA-4 can function as a negative regulator of T cell activation. Immunity1(5), 405–413 (1994).
  • Azuma M, Ito D, Yagita H et al. B70 antigen is a second ligand for CTLA-4 and CD28. Nature366(6450), 76–79 (1993).
  • Greene JL, Leytze GM, Emswiler J et al. Covalent dimerization of CD28/CTLA-4 and oligomerization of CD80/CD86 regulate T cell costimulatory interactions. J. Biol. Chem.271(43), 26762–26771 (1996).
  • Rudd CE, Taylor A, Schneider H. CD28 and CTLA-4 coreceptor expression and signal transduction. Immunol. Rev.229(1), 12–26 (2009).
  • Teft WA, Kirchhof MG, Madrenas J. A molecular perspective of CTLA-4 function. Annu. Rev. Immunol.24, 65–97 (2006).
  • Parry RV, Chemnitz JM, Frauwirth KA et al. CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms. Mol. Cell Biol.25(21), 9543–9553 (2005).
  • Hu H, Rudd CE, Schneider H. Src kinases Fyn and Lck facilitate the accumulation of phosphorylated CTLA-4 and its association with PI-3 kinase in intracellular compartments of T-cells. Biochem. Biophys. Res. Commun.288(3), 573–578 (2001).
  • Bour-Jordan H, Grogan JL, Tang Q et al. CTLA-4 regulates the requirement for cytokine-induced signals in T(h)2 lineage commitment. Nat. Immunol.4(2), 182–188 (2003).
  • Fraser JH, Rincon M, McCoy KD, Le Gros G. CTLA4 ligation attenuates AP-1, NFAT and NF-κB activity in activated T cells. Eur. J. Immunol.29(3), 838–844 (1999).
  • Harlin H, Hwang KW, Palucki DA et al. CTLA-4 engagement regulates NF-κB activation in vivo. Eur J. Immunol.32(8), 2095–2104 (2002).
  • Olsson C, Riesbeck K, Dohlsten M, Michaelsson E. CTLA-4 ligation suppresses CD28-induced NF-κB and AP-1 activity in mouse T cell blasts. J. Biol. Chem.274(20), 14400–14405 (1999).
  • Lee KM, Chuang E, Griffin M et al. Molecular basis of T cell inactivation by CTLA-4. Science282(5397), 2263–2266 (1998).
  • Leach DR, Krummel MF, Allison JP. Enhancement of antitumor immunity by CTLA-4 blockade. Science271(5256), 1734–1736 (1996).
  • Kwon ED, Hurwitz AA, Foster BA et al. Manipulation of T cell costimulatory and inhibitory signals for immunotherapy of prostate cancer. Proc. Natl Acad. Sci. USA94(15), 8099–8103 (1997).
  • Shrikant P, Khoruts A, Mescher MF. CTLA-4 blockade reverses CD8+ T cell tolerance to tumor by a CD4+ T cell- and IL-2-dependent mechanism. Immunity11(4), 483–493 (1999).
  • Sotomayor EM, Borrello I, Tubb E, Allison JP, Levitsky HI. In vivo blockade of CTLA-4 enhances the priming of responsive T cells but fails to prevent the induction of tumor antigen-specific tolerance. Proc. Natl Acad. Sci. USA96(20), 11476–11481 (1999).
  • Yang S, Darrow TL, Seigler HF. Generation of primary tumor-specific cytotoxic T lymphocytes from autologous and human lymphocyte antigen class I-matched allogeneic peripheral blood lymphocytes by B7 gene-modified melanoma cells. Cancer Res.57(8), 1561–1568 (1997).
  • Hurwitz AA, Yu TF, Leach DR, Allison JP. CTLA-4 blockade synergizes with tumor-derived granulocyte-macrophage colony-stimulating factor for treatment of an experimental mammary carcinoma. Proc. Natl Acad. Sci. USA95(17), 10067–10071 (1998).
  • van Elsas A, Hurwitz AA, Allison JP. Combination immunotherapy of B16 melanoma using anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and granulocyte/macrophage colony-stimulating factor (GM-CSF)-producing vaccines induces rejection of subcutaneous and metastatic tumors accompanied by autoimmune depigmentation. J. Exp. Med.190(3), 355–366 (1999).
  • Hurwitz AA, Foster BA, Kwon ED et al. Combination immunotherapy of primary prostate cancer in a transgenic mouse model using CTLA-4 blockade. Cancer Res.60(9), 2444–2448 (2000).
  • Peggs KS, Segal NH, Allison JP. Targeting immunosupportive cancer therapies: accentuate the positive, eliminate the negative. Cancer Cell12(3), 192–199 (2007).
  • Hodi FS, Mihm MC, Soiffer RJ et al. Biologic activity of cytotoxic T lymphocyte-associated antigen 4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patients. Proc. Natl Acad. Sci. USA100(8), 4712–4717 (2003).
  • Weber JS, O’Day S, Urba W et al. Phase I/II study of ipilimumab for patients with metastatic melanoma. J. Clin. Oncol.26(36), 5950–5956 (2008).
  • Maker AV, Yang JC, Sherry RM et al. Intrapatient dose escalation of anti-CTLA-4 antibody in patients with metastatic melanoma. J. Immunother.29(4), 455–463 (2006).
  • Phan GQ, Yang JC, Sherry RM et al. Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma. Proc. Natl Acad. Sci. USA100(14), 8372–8377 (2003).
  • Sanderson K, Scotland R, Lee P et al. Autoimmunity in a Phase I trial of a fully human anti-cytotoxic T-lymphocyte antigen-4 monoclonal antibody with multiple melanoma peptides and montanide ISA 51 for patients with resected stages III and IV melanoma. J. Clin. Oncol.23(4), 741–750 (2005).
  • Weber JS, Hersh EM, Yellin M et al. The efficacy and safety of ipilimumab (MDX-010) in patients with unresectable stage III or stage IV malignant melanoma. J. Clin. Oncol. (25). Proceedings of: 2007 ASCO Annual Meeting Chicago, IL, USA, 1–5 June 2007 (2007) (Abstract 8523).
  • Fong L, Kavanagh B, Hou Y et al. Combination immunotherapy with GM-CSF and CTLA-4 blockade for hormone refractory prostate cancer: balancing the expansion of activated effector and regulatory T cells. J. Clin. Oncol. (25). Proceedings of: 2007 ASCO Annual Meeting. Chicago, IL, USA, 1–5 June 2007 (Abstract 3001).
  • Gerritsen WR, van den Eertwegh AJ, de Gruijt et al. Biochemical and immunologic correlates of clinical response in a combination trial of the GM-CSF-gene transduced allogeneic prostate cancer immunotherapy and ipilimumab in patients with metastatic-hormone-refractory prostate cancer (mHRPC). J. Clin. Oncol. (25). Proceedings of: 2007 ASCO Annual Meeting. Chicago, IL, USA, 1–5 June 2007 (Abstract 5120).
  • Rini BI, Weinberg V, Bok R, Small EJ. Prostate-specific antigen kinetics as a measure of the biologic effect of granulocyte-macrophage colony-stimulating factor in patients with serologic progression of prostate cancer. J. Clin. Oncol.21(1), 99–105 (2003).
  • Small EJ, Higano C, Tchekmedyian N et al. Randomized Phase II study comparing 4 monthly doses of ipilimumab (MDX-010) as a single agent or in combination with a single dose of docetaxel in patients with hormone-refractory prostate cancer. J. Clin. Oncol.(24). Proceedings of: ASCO Annual Meeting (2006) (Abstract 4609).
  • Small EJ, Tchekmedyian NS, Rini BI et al. A pilot trial of CTLA-4 blockade with human anti-CTLA-4 in patients with hormone-refractory prostate cancer. Clin. Cancer Res.13(6), 1810–1815 (2007).
  • Yang JC, Hughes M, Kammula U et al. Ipilimumab (anti-CTLA4 antibody) causes regression of metastatic renal cell cancer associated with enteritis and hypophysitis. J. Immunother.30(8), 825–830 (2007).
  • Ribas A, Camacho LH, Lopez-Berestein G et al. Antitumor activity in melanoma and anti-self responses in a Phase I trial with the anti-cytotoxic T lymphocyte-associated antigen 4 monoclonal antibody CP-675,206. J. Clin. Oncol.23(35), 8968–8977 (2005).
  • Ribas A. Results of a Phase II clinical trial of 2 doses and schedules of CP-675,206, an anti-CTLA4 monoclonal antibody, in patients with advanced melanoma. J. Clin. Oncol. (25). Proceedings of: ASCO Annual Meeting (2007) (Abstract 118).
  • Ribas A. Phase I trial of monthly doses of the human anti-CTLA-4 monoclonal antibody CP-675,206 in patients with advanced malignancies. J. Clin. Oncol. (23). Proceedings of: ASCO Annual Meeting (2005) (Abstract 716).
  • Ribas A. Phase III, open-label, randomized, comparative study of tremelimumab (CP-675,206) and chemotherapy (temozolomide [TMZ] or dacarbazine [DTIC] in patients with advanced melanoma. J. Clin. Oncol. (25). Proceedings of: 2008 Annual Meeting (2008) (Abstract 486).
  • Ishida Y, Agata Y, Shibahara K, Honjo T. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J.11(11), 3887–3895 (1992).
  • Freeman GJ, Long AJ, Iwai Y et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J. Exp. Med.192(7), 1027–1034 (2000).
  • Muhlbauer M, Fleck M, Schutz C et al. PD-L1 is induced in hepatocytes by viral infection and by interferon-α and -γ and mediates T cell apoptosis. J. Hepatol.45(4), 520–528 (2006).
  • Chemnitz JM, Parry RV, Nichols KE, June CH, Riley JL. SHP-1 and SHP-2 associate with immunoreceptor tyrosine-based switch motif of programmed death 1 upon primary human T cell stimulation, but only receptor ligation prevents T cell activation. J. Immunol.173(2), 945–954 (2004).
  • Carter L, Fouser LA, Jussif J et al. PD-1:PD-L inhibitory pathway affects both CD4(+) and CD8(+) T cells and is overcome by IL-2. Eur J. Immunol.32(3), 634–643 (2002).
  • Latchman Y, Wood CR, Chernova T et al. PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nat. Immunol.2(3), 261–268 (2001).
  • Driessens G, Kline J, Gajewski TF. Costimulatory and coinhibitory receptors in anti-tumor immunity. Immunol. Rev.229(1), 126–144 (2009).
  • Nishimura H, Nose M, Hiai H, Minato N, Honjo T. Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity11(2), 141–151 (1999).
  • Nishimura H, Okazaki T, Tanaka Y et al. Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. Science291(5502), 319–322 (2001).
  • Okazaki T, Tanaka Y, Nishio R et al. Autoantibodies against cardiac troponin I are responsible for dilated cardiomyopathy in PD-1-deficient mice. Nat. Med.9(12), 1477–1483 (2003).
  • Hamanishi J, Mandai M, Iwasaki M et al. Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer. Proc. Natl Acad. Sci. USA104(9), 3360–3365 (2007).
  • Inman BA, Sebo TJ, Frigola X et al. PD-L1 (B7-H1) expression by urothelial carcinoma of the bladder and BCG-induced granulomata: associations with localized stage progression. Cancer109(8), 1499–1505 (2007).
  • Thompson RH, Gillett MD, Cheville JC et al. Costimulatory B7-H1 in renal cell carcinoma patients: indicator of tumor aggressiveness and potential therapeutic target. Proc. Natl Acad. Sci. USA101(49), 17174–17179 (2004).
  • Iwai Y, Ishida M, Tanaka Y et al. Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc. Natl Acad. Sci. USA99(19), 12293–12297 (2002).
  • Hirano F, Kaneko K, Tamura H et al. Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity. Cancer Res.65(3), 1089–1096 (2005).
  • Blank C, Brown I, Peterson AC et al. PD-L1/B7H-1 inhibits the effector phase of tumor rejection by T cell receptor (TCR) transgenic CD8+ T cells. Cancer Res.64(3), 1140–1145 (2004).
  • Berger R, Rotem-Yehudar R, Slama G et al. Phase I safety and pharmacokinetic study of CT-011, a humanized antibody interacting with PD-1, in patients with advanced hematologic malignancies. Clin. Cancer Res.14(10), 3044–3051 (2008).
  • Brahmer J, Topalian S, Wollner I et al. Safety and activity of MDX-1106 (ONO-4538), an anti-PD-1 monoclonal antibody, in patients with selected refractory or relapsed malignancies. J. Clin. Oncol. (26). Proceedings of: ASCO Annual Meeting (2006) (Abstract 2006).
  • Brahmer J, Topalian S, Powderly J et al. Phase II experience with MDX-1106 (ONO-4538), an anti-PD-1 monoclonal antibody, in patients with selected refractory or relapsed malignancies. J. Clin. Oncol. (27). Proceedings of: ASCO Annual Meeting (2009) (Abstract 3018).
  • Welters MJ, Piersma SJ, van der Burg SH. T-regulatory cells in tumour-specific vaccination strategies. Expert Opin. Biol. Ther.8(9), 1365–1379 (2008).
  • Sakaguchi S. Naturally arising CD4+ regulatory T cells for immunologic self-tolerance and negative control of immune responses. Annu. Rev. Immunol.22, 531–562 (2004).
  • Caramalho I, Lopes-Carvalho T, Ostler D et al. Regulatory T cells selectively express Toll-like receptors and are activated by lipopolysaccharide. J. Exp. Med.197(4), 403–411 (2003).
  • Curiel TJ. Regulatory T-cell development: is Foxp3 the decider? Nat. Med.13(3), 250–253 (2007).
  • Ono M, Yaguchi H, Ohkura N et al. Foxp3 controls regulatory T-cell function by interacting with AML1/Runx1. Nature446(7136), 685–689 (2007).
  • Wu Y, Borde M, Heissmeyer V et al. FOXP3 controls regulatory T cell function through cooperation with NFAT. Cell126(2), 375–387 (2006).
  • Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science299(5609), 1057–1061 (2003).
  • Wing K, Onishi Y, Prieto-Martin P et al. CTLA-4 control over Foxp3+ regulatory T cell function. Science322(5899), 271–275 (2008).
  • Apostolou I, Verginis P, Kretschmer K et al. Peripherally induced Treg: mode, stability, and role in specific tolerance. J. Clin. Immunol.28(6), 619–624 (2008).
  • Hauben E, Roncarolo MG. Human CD4+ regulatory T cells and activation-induced tolerance. Microbes Infect.7(7–8), 1023–1032 (2005).
  • Jonuleit H, Schmitt E, Schuler G, Knop J, Enk AH. Induction of interleukin 10-producing, nonproliferating CD4(+) T cells with regulatory properties by repetitive stimulation with allogeneic immature human dendritic cells. J. Exp. Med.192(9), 1213–1222 (2000).
  • Groux H, O’Garra A, Bigler M et al. A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature389(6652), 737–742 (1997).
  • Levings MK, Sangregorio R, Galbiati F et al. IFN-α and IL-10 induce the differentiation of human type 1 T regulatory cells. J. Immunol.166(9), 5530–5539 (2001).
  • Roncarolo MG, Gregori S, Battaglia M et al. Interleukin-10-secreting type 1 regulatory T cells in rodents and humans. Immunol. Rev.212, 28–50 (2006).
  • Faria AM, Weiner HL. Oral tolerance and TGF-β-producing cells. Inflamm. Allergy Drug Targets5(3), 179–190 (2006).
  • Weiner HL. Induction and mechanism of action of transforming growth factor-β-secreting Th3 regulatory cells. Immunol. Rev.182, 207–214 (2001).
  • Apostolou I, von Boehmer H. In vivo instruction of suppressor commitment in naive T cells. J. Exp. Med.199(10), 1401–1408 (2004).
  • Larmonier N, Marron M, Zeng Y et al. Tumor-derived CD4(+)CD25(+) regulatory T cell suppression of dendritic cell function involves TGF-β and IL-10. Cancer Immunol. Immunother.56(1), 48–59 (2007).
  • Strauss L, Bergmann C, Szczepanski M et al. A unique subset of CD4+CD25highFoxp3+ T cells secreting interleukin-10 and transforming growth factor-β1 mediates suppression in the tumor microenvironment. Clin. Cancer Res.13(15 Pt 1), 4345–4354 (2007).
  • Bates GJ, Fox SB, Han C et al. Quantification of regulatory T cells enables the identification of high-risk breast cancer patients and those at risk of late relapse. J. Clin. Oncol.24(34), 5373–5380 (2006).
  • Salama P, Phillips M, Grieu F et al. Tumor-infiltrating FOXP3+ T regulatory cells show strong prognostic significance in colorectal cancer. J. Clin. Oncol.27(2), 186–192 (2009).
  • Kobayashi N, Hiraoka N, Yamagami W et al. FOXP3+ regulatory T cells affect the development and progression of hepatocarcinogenesis. Clin. Cancer Res.13(3), 902–911 (2007).
  • Curiel TJ, Coukos G, Zou L et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat. Med.10(9), 942–949 (2004).
  • Wolf D, Wolf AM, Rumpold H et al. The expression of the regulatory T cell-specific forkhead box transcription factor FoxP3 is associated with poor prognosis in ovarian cancer. Clin. Cancer Res.11(23), 8326–8331 (2005).
  • Gao Q, Qiu SJ, Fan J et al. Intratumoral balance of regulatory and cytotoxic T cells is associated with prognosis of hepatocellular carcinoma after resection. J. Clin. Oncol.25(18), 2586–2593 (2007).
  • Jordanova ES, Gorter A, Ayachi O et al. Human leukocyte antigen class I, MHC class I chain-related molecule A, and CD8+/regulatory T-cell ratio: which variable determines survival of cervical cancer patients? Clin. Cancer Res.14(7), 2028–2035 (2008).
  • Baecher-Allan C, Brown JA, Freeman GJ, Hafler DA. CD4+CD25high regulatory cells in human peripheral blood. J. Immunol.167(3), 1245–1253 (2001).
  • Siegmund K, Feuerer M, Siewert C et al. Migration matters: regulatory T-cell compartmentalization determines suppressive activity in vivo. Blood106(9), 3097–3104 (2005).
  • Wei S, Kryczek I, Zou W. Regulatory T-cell compartmentalization and trafficking. Blood108(2), 426–431 (2006).
  • Vieweg J, Su Z, Dahm P, Kusmartsev S. Reversal of tumor-mediated immunosuppression. Clin. Cancer Res.13(2 Pt 2), 727s–732s (2007).
  • Valzasina B, Piconese S, Guiducci C, Colombo MP. Tumor-induced expansion of regulatory T cells by conversion of CD4+CD25- lymphocytes is thymus and proliferation independent. Cancer Res.66(8), 4488–4495 (2006).
  • Zhou G, Drake CG, Levitsky HI. Amplification of tumor-specific regulatory T cells following therapeutic cancer vaccines. Blood107(2), 628–636 (2006).
  • Zhou G, Levitsky HI. Natural regulatory T cells and de novo-induced regulatory T cells contribute independently to tumor-specific tolerance. J. Immunol.178(4), 2155–2162 (2007).
  • Nishikawa H, Kato T, Tawara I et al. Definition of target antigens for naturally occurring CD4(+) CD25(+) regulatory T cells. J. Exp. Med.201(5), 681–686 (2005).
  • Comes A, Rosso O, Orengo AM et al. CD25+ regulatory T cell depletion augments immunotherapy of micrometastases by an IL-21-secreting cellular vaccine. J. Immunol.176(3), 1750–1758 (2006).
  • Golgher D, Jones E, Powrie F, Elliott T, Gallimore A. Depletion of CD25+ regulatory cells uncovers immune responses to shared murine tumor rejection antigens. Eur. J. Immunol.32(11), 3267–3275 (2002).
  • Jones E, Dahm-Vicker M, Simon AK et al. Depletion of CD25+ regulatory cells results in suppression of melanoma growth and induction of autoreactivity in mice. Cancer Immun.2, 1 (2002).
  • Onizuka S, Tawara I, Shimizu J et al. Tumor rejection by in vivo administration of anti-CD25 (interleukin-2 receptor a) monoclonal antibody. Cancer Res.59(13), 3128–3133 (1999).
  • Shimizu J, Yamazaki S, Sakaguchi S. Induction of tumor immunity by removing CD25+CD4+ T cells: a common basis between tumor immunity and autoimmunity. J. Immunol.163(10), 5211–5218 (1999).
  • Sutmuller RP, van Duivenvoorde LM, van Elsas A et al. Synergism of cytotoxic T lymphocyte-associated antigen 4 blockade and depletion of CD25(+) regulatory T cells in antitumor therapy reveals alternative pathways for suppression of autoreactive cytotoxic T lymphocyte responses. J. Exp. Med.194(6), 823–832 (2001).
  • Sandrini S. Use of IL-2 receptor antagonists to reduce delayed graft function following renal transplantation: a review. Clin. Transplant.19(6), 705–710 (2005).
  • Lutsiak ME, Semnani RT, De Pascalis R et al. Inhibition of CD4(+)25+ T regulatory cell function implicated in enhanced immune response by low-dose cyclophosphamide. Blood105(7), 2862–2868 (2005).
  • Ghiringhelli F, Menard C, Terme M et al. CD4+CD25+ regulatory T cells inhibit natural killer cell functions in a transforming growth factor-β-dependent manner. J. Exp. Med.202(8), 1075–1085 (2005).
  • Machiels JP, Reilly RT, Emens LA et al. Cyclophosphamide, doxorubicin, and paclitaxel enhance the antitumor immune response of granulocyte/macrophage–colony stimulating factor-secreting whole-cell vaccines in HER-2/neu tolerized mice. Cancer Res.61(9), 3689–3697 (2001).
  • Zhang H, Chua KS, Guimond M et al. Lymphopenia and interleukin-2 therapy alter homeostasis of CD4+CD25+ regulatory T cells. Nat. Med.11(11), 1238–1243 (2005).
  • Barnett B, Kryczek I, Cheng P, Zou W, Curiel TJ. Regulatory T cells in ovarian cancer: biology and therapeutic potential. Am. J. Reprod. Immunol.54(6), 369–377 (2005).
  • Attia P, Maker AV, Haworth LR, Rogers-Freezer L, Rosenberg SA. 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. J. Immunother.28(6), 582–592 (2005).
  • Dannull J, Su Z, Rizzieri D et al. Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells. J. Clin. Invest.115(12), 3623–3633 (2005).
  • Gnjatic S, Altorki NK, Tang DN et al. NY-ESO-1 DNA vaccine induces T-cell responses that are suppressed by regulatory T cells. Clin. Cancer Res.15(6), 2130–2139 (2009).
  • Bronte V, Serafini P, Apolloni E, Zanovello P. Tumor-induced immune dysfunctions caused by myeloid suppressor cells. J. Immunother.24(6), 431–446 (2001).
  • Gabrilovich D, Ishida T, Oyama T et al. Vascular endothelial growth factor inhibits the development of dendritic cells and dramatically affects the differentiation of multiple hematopoietic lineages in vivo. Blood92(11), 4150–4166 (1998).
  • Kusmartsev SA, Li Y, Chen SH. Gr-1+ myeloid cells derived from tumor-bearing mice inhibit primary T cell activation induced through CD3/CD28 costimulation. J. Immunol.165(2), 779–785 (2000).
  • Kusmartsev S, Nagaraj S, Gabrilovich DI. Tumor-associated CD8+ T cell tolerance induced by bone marrow-derived immature myeloid cells. J. Immunol.175(7), 4583–4592 (2005).
  • Ostrand-Rosenberg S, Sinha P. Myeloid-derived suppressor cells: linking inflammation and cancer. J. Immunol.182(8), 4499–4506 (2009).
  • Bronte V, Serafini P, De Santo C et al. IL-4-induced arginase 1 suppresses alloreactive T cells in tumor-bearing mice. J. Immunol.170(1), 270–278 (2003).
  • Corzo CA, Cotter MJ, Cheng P et al. Mechanism regulating reactive oxygen species in tumor-induced myeloid-derived suppressor cells. J. Immunol.182(9), 5693–5701 (2009).
  • Kusmartsev S, Nefedova Y, Yoder D, Gabrilovich DI. Antigen-specific inhibition of CD8+ T cell response by immature myeloid cells in cancer is mediated by reactive oxygen species. J. Immunol.172(2), 989–999 (2004).
  • Nagaraj S, Gupta K, Pisarev V et al. Altered recognition of antigen is a mechanism of CD8+ T-cell tolerance in cancer. Nat. Med.13(7), 828–835 (2007).
  • Huang B, Pan PY, Li Q et al. Gr-1+CD115+ immature myeloid suppressor cells mediate the development of tumor-induced T regulatory cells and T-cell anergy in tumor-bearing host. Cancer Res.66(2), 1123–1131 (2006).
  • Serafini P, Mgebroff S, Noonan K, Borrello I. Myeloid-derived suppressor cells promote cross-tolerance in B-cell lymphoma by expanding regulatory T cells. Cancer Res.68(13), 5439–5449 (2008).
  • Sinha P, Clements VK, Bunt SK, Albelda SM, Ostrand-Rosenberg S. Cross-talk between myeloid-derived suppressor cells and macrophages subverts tumor immunity toward a type 2 response. J. Immunol.179(2), 977–983 (2007).
  • Filipazzi P, Valenti R, Huber V et al. Identification of a new subset of myeloid suppressor cells in peripheral blood of melanoma patients with modulation by a granulocyte-macrophage colony-stimulation factor-βased antitumor vaccine. J. Clin. Oncol.25(18), 2546–2553 (2007).
  • Mirza N, Fishman M, Fricke I et al. All-trans-retinoic acid improves differentiation of myeloid cells and immune response in cancer patients. Cancer Res.66(18), 9299–9307 (2006).
  • Srivastava MK, Bosch JJ, Thompson JA et al. Lung cancer patients’ CD4(+) T cells are activated in vitro by MHC II cell-based vaccines despite the presence of myeloid-derived suppressor cells. Cancer Immunol. Immunother.57(10), 1493–1504 (2008).
  • Zea AH, Rodriguez PC, Atkins MB et al. Arginase-producing myeloid suppressor cells in renal cell carcinoma patients: a mechanism of tumor evasion. Cancer Res.65(8), 3044–3048 (2005).
  • Terabe M, Matsui S, Park JM et al. Transforming growth factor-β production and myeloid cells are an effector mechanism through which CD1d-restricted T cells block cytotoxic T lymphocyte-mediated tumor immunosurveillance: abrogation prevents tumor recurrence. J. Exp. Med.198(11), 1741–1752 (2003).
  • Bronte V, Apolloni E, Cabrelle A et al. Identification of a CD11b(+)/Gr-1(+)/CD31(+) myeloid progenitor capable of activating or suppressing CD8(+) T cells. Blood96(12), 3838–3846 (2000).
  • Kusmartsev S, Gabrilovich DI. Inhibition of myeloid cell differentiation in cancer: the role of reactive oxygen species. J. Leukoc. Biol.74(2), 186–196 (2003).
  • Kusmartsev S, Cheng F, Yu B et al. All-trans-retinoic acid eliminates immature myeloid cells from tumor-bearing mice and improves the effect of vaccination. Cancer Res.63(15), 4441–4449 (2003).
  • De Santo C, Serafini P, Marigo I et al. Nitroaspirin corrects immune dysfunction in tumor-bearing hosts and promotes tumor eradication by cancer vaccination. Proc. Natl Acad. Sci. USA102(11), 4185–4190 (2005).
  • Smyth MJ, Dunn GP, Schreiber RD. Cancer immunosurveillance and immunoediting: the roles of immunity in suppressing tumor development and shaping tumor immunogenicity. Adv. Immunol.90, 1–50 (2006).
  • Liakou CI, Kamat A, Tang DN et al. CTLA-4 blockade increases IFNg-producing CD4+ICOShi cells to shift the ratio of effector to regulatory T cells in cancer patients. Proc. Natl Acad. Sci. USA105(39), 14987–14992 (2008).
  • Saenger YM, Wolchok JD. The heterogeneity of the kinetics of response to ipilimumab in metastatic melanoma: patient cases. Cancer Immun.8, 1 (2008).
  • Van der Burg SH. Therapeutic vaccines in cancer: moving from immunomonitoring to immunoguiding. Expert Rev. Vaccines7(1), 1–5 (2008).

Websites

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.