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References
Hao,Y., Legrand,N., & Freitas,A.A. (2006) The clone size of peripheral CD8 T cells is regulated by TCR promiscuity. J.Exp.Med.
Watanabe,N., Gavrieli,M., Sedy,J.R., Yang,J., Fallarino,F., Loftin,S.K., Hurchla,M.A., Zimmerman,N., Sim,J., Zang,X., Murphy,T.L., Russell,J.H., Allison,J.P., & Murphy,K.M. (2003) BTLA is a lymphocyte inhibitory receptor with similarities to CTLA-4 and PD-1. Nat.Immunol., 4, 670–679.
Marrogi,A.J., Munshi,A., Merogi,A.J., Ohadike,Y., El Habashi,A., Marrogi,O.L., & Freeman,S.M. (1997) Study of tumor infiltrating lymphocytes and transforming growth factor-beta as prognostic factors in breast carcinoma. Int.J.Cancer, 74, 492–501.
Zhang,L., Conejo-Garcia,J.R., Katsaros,D., Gimotty,P.A., Massobrio,M., Regnani,G., Makrigiannakis,A., Gray,H., Schlienger,K., Liebman,M.N., Rubin,S.C., & Coukos,G. (2003) Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N.Engl.J.Med., 348, 203–213.
Nakano,O., Sato,M., Naito,Y., Suzuki,K., Orikasa,S., Aizawa,M., Suzuki,Y., Shintaku,I., Nagura,H., & Ohtani,H. (2001) Proliferative activity of intratumoral CD8(+) T-lymphocytes as a prognostic factor in human renal cell carcinoma: clinicopathologic demonstration of antitumor immunity. Cancer Res., 61, 5132–5136.
Vesalainen,S., Lipponen,P., Talja,M., & Syrjanen,K. (1994) Histological grade, perineural infiltration, tumour-infiltrating lymphocytes and apoptosis as determinants of long-term prognosis in prostatic adenocarcinoma. Eur.J.Cancer, 30A, 1797–1803.
Naito,Y., Saito,K., Shiiba,K., Ohuchi,A., Saigenji,K., Nagura,H., & Ohtani,H. (1998) CD8+ T cells infiltrated within cancer cell nests as a prognostic factor in human colorectal cancer. Cancer Res., 58, 3491–3494.
Mortarini,R., Piris,A., Maurichi,A., Molla,A., Bersani,I., Bono,A., Bartoli,C., Santinami,M., Lombardo,C., Ravagnani,F., Cascinelli,N., Parmiani,G., & Anichini,A. (2003) Lack of terminally differentiated tumor-specific CD8+ T cells at tumor site in spite of antitumor immunity to self-antigens in human metastatic melanoma. Cancer Res., 63, 2535–2545.
Gabrilovich,D. (2004) Mechanisms and functional significance of tumour-induced dendritic-cell defects. Nat.Rev.Immunol., 4, 941–952.
Furumoto,K., Soares,L., Engleman,E.G., & Merad,M. (2004) Induction of potent antitumor immunity by in situ targeting of intratumoral DCs. J.Clin.Invest, 113, 774–783.
Young,J.W. & Inaba,K. (1996) Dendritic cells as adjuvants for class I major histocompatibility complex-restricted antitumor immunity. J.Exp.Med., 183, 7–11.
Dranoff,G., Jaffee,E., Lazenby,A., Golumbek,P., Levitsky,H., Brose,K., Jackson,V., Hamada,H., Pardoll,D., & Mulligan,R.C. (1993) Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc.Natl.Acad.Sci.U.S.A, 90, 3539–3543.
Finn,O.J. (2003) Cancer vaccines: between the idea and the reality. Nat.Rev.Immunol., 3, 630–641.
Rosenberg,S.A., Yang,J.C., & Restifo,N.P. (2004) Cancer immunotherapy: moving beyond current vaccines. Nat.Med., 10, 909–915.
Rosenberg,S.A., Sherry,R.M., Morton,K.E., Scharfman,W.J., Yang,J.C., Topalian,S.L., Royal,R.E., Kammula,U., Restifo,N.P., Hughes,M.S., Schwartzentruber,D., Berman,D.M., Schwarz,S.L., Ngo,L.T., Mavroukakis,S.A., White,D.E., & Steinberg,S.M. (2005) 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, 6169–6176.
Nishikawa,H., Qian,F., Tsuji,T., Ritter,G., Old,L.J., Gnjatic,S., & Odunsi,K. (2006) Influence of CD4+CD25+ regulatory T cells on low/high-avidity CD4+ T cells following peptide vaccination. J.Immunol., 176, 6340–6346.
Dhodapkar,M.V., Steinman,R.M., Krasovsky,J., Munz,C., & Bhardwaj,N. (2001) Antigen-specific inhibition of effector T cell function in humans after injection of immature dendritic cells. J.Exp.Med., 193, 233–238.
Chakraborty,N.G., Chattopadhyay,S., Mehrotra,S., Chhabra,A., & Mukherji,B. (2004) Regulatory T-cell response and tumor vaccine-induced cytotoxic T lymphocytes in human melanoma. Hum.Immunol., 65, 794–802.
Thompson,R.H., Gillett,M.D., Cheville,J.C., Lohse,C.M., Dong,H., Webster,W.S., Krejci,K.G., Lobo,J.R., Sengupta,S., Chen,L., Zincke,H., Blute,M.L., Strome,S.E., Leibovich,B.C., & Kwon,E.D. (2004) Costimulatory B7-H1 in renal cell carcinoma patients: Indicator of tumor aggressiveness and potential therapeutic target. Proc.Natl.Acad.Sci.U.S.A, 101, 17174–17179.
Blank,C., Brown,I., Peterson,A.C., Spiotto,M., Iwai,Y., Honjo,T., & Gajewski,T.F. (2004) PD-L1/B7H-1 inhibits the effector phase of tumor rejection by T cell receptor (TCR) transgenic CD8+ T cells. Cancer Res., 64, 1140–1145.
Harding,F.A., McArthur,J.G., Gross,J.A., Raulet,D.H., & Allison,J.P. (1992) CD28-mediated signalling co-stimulates murine T cells and prevents induction of anergy in T-cell clones. Nature, 356, 607–609.
Linsley,P.S., Brady,W., Grosmaire,L., Aruffo,A., Damle,N.K., & Ledbetter,J.A. (1991) Binding of the B cell activation antigen B7 to CD28 costimulates T cell proliferation and interleukin 2 mRNA accumulation. J.Exp.Med., 173, 721–730.
Hathcock,K.S., Laszlo,G., Pucillo,C., Linsley,P., & Hodes,R.J. (1994) Comparative analysis of B7–1 and B7–2 costimulatory ligands: expression and function. J.Exp.Med., 180, 631–640.
Lenschow,D.J. & Bluestone,J.A. (1993) T cell co-stimulation and in vivo tolerance. Curr.Opin.Immunol., 5, 747–752.
Fallarino,F., Grohmann,U., Hwang,K.W., Orabona,C., Vacca,C., Bianchi,R., Belladonna,M.L., Fioretti,M.C., Alegre,M.L., & Puccetti,P. (2003) Modulation of tryptophan catabolism by regulatory T cells. Nat.Immunol., 4, 1206–1212.
Shahinian,A., Pfeffer,K., Lee,K.P., Kundig,T.M., Kishihara,K., Wakeham,A., Kawai,K., Ohashi,P.S., Thompson,C.B., & Mak,T.W. (1993) Differential T cell costimulatory requirements in CD28-deficient mice. Science, 261, 609–612.
Borriello,F., Sethna,M.P., Boyd,S.D., Schweitzer,A.N., Tivol,E.A., Jacoby,D., Strom,T.B., Simpson,E.M., Freeman,G.J., & Sharpe,A.H. (1997) B7–1 and B7–2 have overlapping, critical roles in immunoglobulin class switching and germinal center formation. Immunity., 6, 303–313.
Diehn,M., Alizadeh,A.A., Rando,O.J., Liu,C.L., Stankunas,K., Botstein,D., Crabtree,G.R., & Brown,P.O. (2002) Genomic expression programs and the integration of the CD28 costimulatory signal in T cell activation. Proc.Natl.Acad.Sci.U.S.A, 99, 11796–11801.
Riley,J.L., Mao,M., Kobayashi,S., Biery,M., Burchard,J., Cavet,G., Gregson,B.P., June,C.H., & Linsley,P.S. (2002) Modulation of TCR-induced transcriptional profiles by ligation of CD28, ICOS, and CTLA-4 receptors. Proc.Natl.Acad.Sci.U.S.A, 99, 11790–11795.
Viola,A. & Lanzavecchia,A. (1996) T cell activation determined by T cell receptor number and tunable thresholds. Science, 273, 104–106.
Waterhouse,P., Penninger,J.M., Timms,E., Wakeham,A., Shahinian,A., Lee,K.P., Thompson,C.B., Griesser,H., & Mak,T.W. (1995) Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. Science, 270, 985–988.
Tivol,E.A., Borriello,F., Schweitzer,A.N., Lynch,W.P., Bluestone,J.A., & Sharpe,A.H. (1995) Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity., 3, 541–547.
Chambers,C.A., Sullivan,T.J., & Allison,J.P. (1997) Lymphoproliferation in CTLA-4-deficient mice is mediated by costimulation-dependent activation of CD4+ T cells. Immunity., 7, 885–895.
Blair,P.J., Riley,J.L., Levine,B.L., Lee,K.P., Craighead,N., Francomano,T., Perfetto,S.J., Gray,G.S., Carreno,B.M., & June,C.H. (1998) CTLA-4 ligation delivers a unique signal to resting human CD4 T cells that inhibits interleukin-2 secretion but allows Bcl-X(L) induction. J.Immunol., 160, 12–15.
Brunner,M.C., Chambers,C.A., Chan,F.K., Hanke,J., Winoto,A., & Allison,J.P. (1999) CTLA-4-Mediated inhibition of early events of T cell proliferation. J.Immunol., 162, 5813–5820.
Egen,J.G. & Allison,J.P. (2002) Cytotoxic T lymphocyte antigen-4 accumulation in the immunological synapse is regulated by TCR signal strength. Immunity., 16, 23–35.
Shiratori,T., Miyatake,S., Ohno,H., Nakaseko,C., Isono,K., Bonifacino,J.S., & Saito,T. (1997) Tyrosine phosphorylation controls internalization of CTLA-4 by regulating its interaction with clathrin-associated adaptor complex AP-2. Immunity., 6, 583–589.
van der Merwe,P.A. & Davis,S.J. (2003) Molecular interactions mediating T cell antigen recognition. Annu.Rev.Immunol., 21, 659–684.
Stamper,C.C., Zhang,Y., Tobin,J.F., Erbe,D.V., Ikemizu,S., Davis,S.J., Stahl,M.L., Seehra,J., Somers,W.S., & Mosyak,L. (2001) Crystal structure of the B7–1/CTLA-4 complex that inhibits human immune responses. Nature, 410, 608–611.
Greene,J.L., Leytze,G.M., Emswiler,J., Peach,R., Bajorath,J., Cosand,W., & Linsley,P.S. (1996) Covalent dimerization of CD28/CTLA-4 and oligomerization of CD80/CD86 regulate T cell costimulatory interactions. J.Biol.Chem., 271, 26762–26771.
Nakaseko,C., Miyatake,S., Iida,T., Hara,S., Abe,R., Ohno,H., Saito,Y., & Saito,T. (1999) Cytotoxic T lymphocyte antigen 4 (CTLA-4) engagement delivers an inhibitory signal through the membrane-proximal region in the absence of the tyrosine motif in the cytoplasmic tail. J.Exp.Med., 190, 765–774.
Carreno,B.M., Bennett,F., Chau,T.A., Ling,V., Luxenberg,D., Jussif,J., Baroja,M.L., & Madrenas,J. (2000) CTLA-4 (CD152) can inhibit T cell activation by two different mechanisms depending on its level of cell surface expression. J.Immunol., 165, 1352–1356.
Masteller,E.L., Chuang,E., Mullen,A.C., Reiner,S.L., & Thompson,C.B. (2000) Structural analysis of CTLA-4 function in vivo. J.Immunol., 164, 5319–5327.
Chikuma,S., Abbas,A.K., & Bluestone,J.A. (2005) B7-independent inhibition of T cells by CTLA-4. J.Immunol., 175, 177–181.
Takahashi,S., Kataoka,H., Hara,S., Yokosuka,T., Takase,K., Yamasaki,S., Kobayashi,W., Saito,Y., & Saito,T. (2005) In vivo overexpression of CTLA-4 suppresses lymphoproliferative diseases and thymic negative selection. Eur.J.Immunol., 35, 399–407.
Vijayakrishnan,L., Slavik,J.M., Illes,Z., Greenwald,R.J., Rainbow,D., Greve,B., Peterson,L.B., Hafler,D.A., Freeman,G.J., Sharpe,A.H., Wicker,L.S., & Kuchroo,V.K. (2004) An autoimmune disease-associated CTLA-4 splice variant lacking the B7 binding domain signals negatively in T cells. Immunity., 20, 563–575.
Chambers,C.A., Sullivan,T.J., Truong,T., & Allison,J.P. (1998) Secondary but not primary T cell responses are enhanced in CTLA-4-deficient CD8+ T cells. Eur.J.Immunol., 28, 3137–3143.
Chambers,C.A., Kuhns,M.S., & Allison,J.P. (1999) Cytotoxic T lymphocyte antigen-4 (CTLA-4) regulates primary and secondary peptide-specific CD4(+) T cell responses. Proc.Natl.Acad.Sci.U.S.A, 96, 8603–8608.
Luhder,F., Chambers,C., Allison,J.P., Benoist,C., & Mathis,D. (2000) Pinpointing when T cell costimulatory receptor CTLA-4 must be engaged to dampen diabetogenic T cells. Proc.Natl.Acad.Sci.U.S.A, 97, 12204–12209.
Greenwald,R.J., Boussiotis,V.A., Lorsbach,R.B., Abbas,A.K., & Sharpe,A.H. (2001) CTLA-4 regulates induction of anergy in vivo. Immunity., 14, 145–155.
Probst,H.C., McCoy,K., Okazaki,T., Honjo,T., & van den,B.M. (2005) Resting dendritic cells induce peripheral CD8+ T cell tolerance through PD-1 and CTLA-4. Nat.Immunol., 6, 280–286.
Leach,D.R., Krummel,M.F., & Allison,J.P. (1996) Enhancement of antitumor immunity by CTLA-4 blockade. Science, 271, 1734–1736.
Yang,Y.F., Zou,J.P., Mu,J., Wijesuriya,R., Ono,S., Walunas,T., Bluestone,J., Fujiwara,H., & Hamaoka,T. (1997) Enhanced induction of antitumor T-cell responses by cytotoxic T lymphocyte-associated molecule-4 blockade: the effect is manifested only at the restricted tumor-bearing stages. Cancer Res., 57, 4036–4041.
Kwon,E.D., Hurwitz,A.A., Foster,B.A., Madias,C., Feldhaus,A.L., Greenberg,N.M., Burg,M.B., & Allison,J.P. (1997) Manipulation of T cell costimulatory and inhibitory signals for immunotherapy of prostate cancer. Proc.Natl.Acad.Sci.U.S.A, 94, 8099–8103.
Shrikant,P., Khoruts,A., & Mescher,M.F. (1999) CTLA-4 blockade reverses CD8+ T cell tolerance to tumor by a CD4+ T cell- and IL-2-dependent mechanism. Immunity., 11, 483–493.
Sotomayor,E.M., Borrello,I., Tubb,E., Allison,J.P., & Levitsky,H.I. (1999) 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.U.S.A, 96, 11476–11481.
van Elsas,A., Hurwitz,A.A., & Allison,J.P. (1999) 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, 355–366.
Hurwitz,A.A., Yu,T.F., Leach,D.R., & Allison,J.P. (1998) CTLA-4 blockade synergizes with tumor-derived granulocyte-macrophage colony-stimulating factor for treatment of an experimental mammary carcinoma. Proc.Natl.Acad.Sci.U.S.A, 95, 10067–10071.
Hurwitz,A.A., Foster,B.A., Kwon,E.D., Truong,T., Choi,E.M., Greenberg,N.M., Burg,M.B., & Allison,J.P. (2000) Combination immunotherapy of primary prostate cancer in a transgenic mouse model using CTLA-4 blockade. Cancer Res., 60, 2444–2448.
Gregor,P.D., Wolchok,J.D., Ferrone,C.R., Buchinshky,H., Guevara-Patino,J.A., Perales,M.A., Mortazavi,F., Bacich,D., Heston,W., Latouche,J.B., Sadelain,M., Allison,J.P., Scher,H.I., & Houghton,A.N. (2004) CTLA-4 blockade in combination with xenogeneic DNA vaccines enhances T-cell responses, tumor immunity and autoimmunity to self antigens in animal and cellular model systems. Vaccine, 22, 1700–1708.
Demaria,S., Kawashima,N., Yang,A.M., Devitt,M.L., Babb,J.S., Allison,J.P., & Formenti,S.C. (2005) Immune-mediated inhibition of metastases after treatment with local radiation and CTLA-4 blockade in a mouse model of breast cancer. Clin.Cancer Res., 11, 728–734.
Mokyr,M.B., Kalinichenko,T., Gorelik,L., & Bluestone,J.A. (1998) Realization of the therapeutic potential of CTLA-4 blockade in low-dose chemotherapy-treated tumor-bearing mice. Cancer Res., 58, 5301–5304.
Davila,E., Kennedy,R., & Celis,E. (2003) Generation of antitumor immunity by cytotoxic T lymphocyte epitope peptide vaccination, CpG-oligodeoxynucleotide adjuvant, and CTLA-4 blockade. Cancer Res., 63, 3281–3288.
Ko,K., Yamazaki,S., Nakamura,K., Nishioka,T., Hirota,K., Yamaguchi,T., Shimizu,J., Nomura,T., Chiba,T., & Sakaguchi,S. (2005) Treatment of advanced tumors with agonistic anti-GITR mAb and its effects on tumor-infiltrating Foxp3+CD25+CD4+ regulatory T cells. J.Exp.Med., 202, 885–891.
Sutmuller,R.P., van Duivenvoorde,L.M., van Elsas,A., Schumacher,T.N., Wildenberg,M.E., Allison,J.P., Toes,R.E., Offringa,R., & Melief,C.J. (2001) 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, 823–832.
Woo,E.Y., Chu,C.S., Goletz,T.J., Schlienger,K., Yeh,H., Coukos,G., Rubin,S.C., Kaiser,L.R., & 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 Res., 61, 4766–4772.
Woo,E.Y., Yeh,H., Chu,C.S., Schlienger,K., Carroll,R.G., Riley,J.L., Kaiser,L.R., & June,C.H. (2002) Cutting edge: Regulatory T cells from lung cancer patients directly inhibit autologous T cell proliferation. J.Immunol., 168, 4272–4276.
Liyanage,U.K., Moore,T.T., Joo,H.G., Tanaka,Y., Herrmann,V., Doherty,G., Drebin,J.A., Strasberg,S.M., Eberlein,T.J., Goedegebuure,P.S., & Linehan,D.C. (2002) Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma. J.Immunol., 169, 2756–2761.
Curiel,T.J., Coukos,G., Zou,L., Alvarez,X., Cheng,P., Mottram,P., Evdemon-Hogan,M., Conejo-Garcia,J.R., Zhang,L., Burow,M., Zhu,Y., Wei,S., Kryczek,I., Daniel,B., Gordon,A., Myers,L., Lackner,A., Disis,M.L., Knutson,K.L., Chen,L., & Zou,W. (2004) Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat.Med., 10, 942–949.
Viguier,M., Lemaitre,F., Verola,O., Cho,M.S., Gorochov,G., Dubertret,L., Bachelez,H., Kourilsky,P., & Ferradini,L. (2004) Foxp3 expressing CD4+CD25(high) regulatory T cells are overrepresented in human metastatic melanoma lymph nodes and inhibit the function of infiltrating T cells. J.Immunol., 173, 1444–1453.
Groux,H., O’Garra,A., Bigler,M., Rouleau,M., Antonenko,S., de Vries,J.E., & Roncarolo,M.G. (1997) A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature, 389, 737–742.
Levings,M.K., Sangregorio,R., Galbiati,F., Squadrone,S., de Waal,M.R., & Roncarolo,M.G. (2001a) IFN-alpha and IL-10 induce the differentiation of human type 1 T regulatory cells. J.Immunol., 166, 5530–5539.
Weiner,H.L. (2001) Induction and mechanism of action of transforming growth factor-beta-secreting Th3 regulatory cells. Immunol.Rev., 182, 207–214.
Walker,M.R., Kasprowicz,D.J., Gersuk,V.H., Benard,A., Van Landeghen,M., Buckner,J.H., & Ziegler,S.F. (2003) Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+. J.Clin.Invest, 112, 1437–1443.
Chen,W., Jin,W., Hardegen,N., Lei,K.J., Li,L., Marinos,N., McGrady,G., & Wahl,S.M. (2003) Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J.Exp.Med., 198, 1875–1886.
Apostolou,I. & von Boehmer,H. (2004) In vivo instruction of suppressor commitment in naive T cells. J.Exp.Med., 199, 1401–1408.
Kretschmer,K., Apostolou,I., Hawiger,D., Khazaie,K., Nussenzweig,M.C., & von Boehmer,H. (2005) Inducing and expanding regulatory T cell populations by foreign antigen. Nat.Immunol., 6, 1219–1227.
Curotto de Lafaille,M.A., Lino,A.C., Kutchukhidze,N., & Lafaille,J.J. (2004) CD25- T cells generate CD25+Foxp3+ regulatory T cells by peripheral expansion. J.Immunol., 173, 7259–7268.
Zhou,G., Drake,C.G., & Levitsky,H.I. (2005) Amplification of tumor-specific regulatory T cells following therapeutic cancer vaccines. Blood.
Gilliet,M. & Liu,Y.J. (2002) Generation of human CD8 T regulatory cells by CD40 ligand-activated plasmacytoid dendritic cells. J.Exp.Med., 195, 695–704.
Zheng,S.G., Wang,J.H., Koss,M.N., Quismorio,F., Jr., Gray,J.D., & Horwitz,D.A. (2004) CD4+ and CD8+ regulatory T cells generated ex vivo with IL-2 and TGF-beta suppress a stimulatory graft-versus-host disease with a lupus-like syndrome. J.Immunol., 172, 1531–1539.
Chang,C.C., Ciubotariu,R., Manavalan,J.S., Yuan,J., Colovai,A.I., Piazza,F., Lederman,S., Colonna,M., Cortesini,R., Dalla-Favera,R., & Suciu-Foca,N. (2002) Tolerization of dendritic cells by T(S) cells: the crucial role of inhibitory receptors ILT3 and ILT4. Nat.Immunol., 3, 237–243.
Noble,A., Giorgini,A., & Leggat,J.A. (2006) Cytokine-induced IL-10-secreting CD8 T cells represent a phenotypically distinct suppressor T-cell lineage. Blood, 107, 4475–4483.
Shimizu,J., Yamazaki,S., & Sakaguchi,S. (1999) Induction of tumor immunity by removing CD25+CD4+ T cells: a common basis between tumor immunity and autoimmunity. J.Immunol., 163, 5211–5218.
Marshall,N.A., Christie,L.E., Munro,L.R., Culligan,D.J., Johnston,P.W., Barker,R.N., & Vickers,M.A. (2004) Immunosuppressive regulatory T cells are abundant in the reactive lymphocytes of Hodgkin lymphoma. Blood, 103, 1755–1762.
Alvaro,T., Lejeune,M., Salvado,M.T., Bosch,R., Garcia,J.F., Jaen,J., Banham,A.H., Roncador,G., Montalban,C., & Piris,M.A. (2005) Outcome in Hodgkin’s lymphoma can be predicted from the presence of accompanying cytotoxic and regulatory T cells. Clin.Cancer Res., 11, 1467–1473.
Dave,S.S., Wright,G., Tan,B., Rosenwald,A., Gascoyne,R.D., Chan,W.C., Fisher,R.I., Braziel,R.M., Rimsza,L.M., Grogan,T.M., Miller,T.P., LeBlanc,M., Greiner,T.C., Weisenburger,D.D., Lynch,J.C., Vose,J., Armitage,J.O., Smeland,E.B., Kvaloy,S., Holte,H., Delabie,J., Connors,J.M., Lansdorp,P.M., Ouyang,Q., Lister,T.A., Davies,A.J., Norton,A.J., Muller-Hermelink,H.K., Ott,G., Campo,E., Montserrat,E., Wilson,W.H., Jaffe,E.S., Simon,R., Yang,L., Powell,J., Zhao,H., Goldschmidt,N., Chiorazzi,M., & Staudt,L.M. (2004) Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells. N.Engl.J.Med., 351, 2159–2169.
Furtado,G.C., Curotto de Lafaille,M.A., Kutchukhidze,N., & Lafaille,J.J. (2002) Interleukin 2 signaling is required for CD4(+) regulatory T cell function. J.Exp.Med., 196, 851–857.
Almeida,A.R., Legrand,N., Papiernik,M., & Freitas,A.A. (2002) Homeostasis of peripheral CD4+ T cells: IL-2R alpha and IL-2 shape a population of regulatory cells that controls CD4+ T cell numbers. J.Immunol., 169, 4850–4860.
Malek,T.R. & Bayer,A.L. (2004) Tolerance, not immunity, crucially depends on IL-2. Nat.Rev.Immunol., 4, 665–674.
Zhang,H., Chua,K.S., Guimond,M., Kapoor,V., Brown,M.V., Fleisher,T.A., Long,L.M., Bernstein,D., Hill,B.J., Douek,D.C., Berzofsky,J.A., Carter,C.S., Read,E.J., Helman,L.J., & Mackall,C.L. (2005) Lymphopenia and interleukin-2 therapy alter homeostasis of CD4+CD25+ regulatory T cells. Nat.Med., 11, 1238–1243.
Ahmadzadeh,M. & Rosenberg,S.A. (2006) IL-2 administration increases CD4+ CD25(hi) Foxp3+ regulatory T cells in cancer patients. Blood, 107, 2409–2414.
Zou,W. (2006) Regulatory T cells, tumour immunity and immunotherapy. Nat.Rev.Immunol., 6, 295–307.
Zhou,G., Drake,C.G., & Levitsky,H.I. (2006) Amplification of tumor-specific regulatory T cells following therapeutic cancer vaccines. Blood, 107, 628–636.
Yamazaki,S., Iyoda,T., Tarbell,K., Olson,K., Velinzon,K., Inaba,K., & Steinman,R.M. (2003) Direct expansion of functional CD25+ CD4+ regulatory T cells by antigen-processing dendritic cells. J.Exp.Med., 198, 235–247.
Thornton,A.M. & Shevach,E.M. (2000) Suppressor effector function of CD4+CD25+ immunoregulatory T cells is antigen nonspecific. J.Immunol., 164, 183–190.
Piccirillo,C.A., Letterio,J.J., Thornton,A.M., McHugh,R.S., Mamura,M., Mizuhara,H., & Shevach,E.M. (2002) CD4(+)CD25(+) regulatory T cells can mediate suppressor function in the absence of transforming growth factor beta1 production and responsiveness. J.Exp.Med., 196, 237–246.
Stephens,L.A., Mottet,C., Mason,D., & Powrie,F. (2001) Human CD4(+)CD25(+) thymocytes and peripheral T cells have immune suppressive activity in vitro. Eur.J.Immunol., 31, 1247–1254.
Asseman,C., Mauze,S., Leach,M.W., Coffman,R.L., & Powrie,F. (1999) An essential role for interleukin 10 in the function of regulatory T cells that inhibit intestinal inflammation. J.Exp.Med., 190, 995–1004.
Suri-Payer,E. & Cantor,H. (2001) Differential cytokine requirements for regulation of autoimmune gastritis and colitis by CD4(+)CD25(+) T cells. J.Autoimmun., 16, 115–123.
Chen,M.L., Pittet,M.J., Gorelik,L., Flavell,R.A., Weissleder,R., von Boehmer,H., & Khazaie,K. (2005) Regulatory T cells suppress tumor-specific CD8 T cell cytotoxicity through TGF-beta signals in vivo. Proc.Natl.Acad.Sci.U.S.A, 102, 419–424.
Green,E.A., Gorelik,L., McGregor,C.M., Tran,E.H., & Flavell,R.A. (2003) CD4+CD25+ T regulatory cells control anti-islet CD8+ T cells through TGF-beta-TGF-beta receptor interactions in type 1 diabetes. Proc.Natl.Acad.Sci.U.S.A, 100, 10878–10883.
Fahlen,L., Read,S., Gorelik,L., Hurst,S.D., Coffman,R.L., Flavell,R.A., & Powrie,F. (2005) T cells that cannot respond to TGF-beta escape control by CD4+CD25+ regulatory T cells. J.Exp.Med., 201, 737–746.
Read,S., Malmstrom,V., & Powrie,F. (2000) Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25(+)CD4(+) regulatory cells that control intestinal inflammation. J.Exp.Med., 192, 295–302.
Takahashi,T., Tagami,T., Yamazaki,S., Uede,T., Shimizu,J., Sakaguchi,N., Mak,T.W., & Sakaguchi,S. (2000) Immunologic self-tolerance maintained by CD25(+)CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4. J.Exp.Med., 192, 303–310.
Bachmann,M.F., Kohler,G., Ecabert,B., Mak,T.W., & Kopf,M. (1999) Cutting edge: lymphoproliferative disease in the absence of CTLA-4 is not T cell autonomous. J.Immunol., 163, 1128–1131.
Kataoka,H., Takahashi,S., Takase,K., Yamasaki,S., Yokosuka,T., Koike,T., & Saito,T. (2005) CD25(+)CD4(+) regulatory T cells exert in vitro suppressive activity independent of CTLA-4. Int.Immunol., 17, 421–427.
Tang,Q., Boden,E.K., Henriksen,K.J., Bour-Jordan,H., Bi,M., & Bluestone,J.A. (2004) Distinct roles of CTLA-4 and TGF-beta in CD4+CD25+ regulatory T cell function. Eur.J.Immunol., 34, 2996–3005.
Quezada,S.A., Peggs,K.S., Curran,M.A., & Allison,J.P. (2006) CTLA4 blockade and GM-CSF combination immunotherapy alters the intratumor balance of effector and regulatory T cells. J.Clin.Invest, 116, 1935–1945.
Thornton,A.M. & Shevach,E.M. (1998) CD4+CD25+ immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production. J.Exp.Med., 188, 287–296.
Chai,J.G., Tsang,J.Y., Lechler,R., Simpson,E., Dyson,J., & Scott,D. (2002) CD4+CD25+ T cells as immunoregulatory T cells in vitro. Eur.J.Immunol., 32, 2365–2375.
Levings,M.K., Sangregorio,R., & Roncarolo,M.G. (2001b) Human cd25(+)cd4(+) t regulatory cells suppress naive and memory T cell proliferation and can be expanded in vitro without loss of function. J.Exp.Med., 193, 1295–1302.
Annunziato,F., Cosmi,L., Liotta,F., Lazzeri,E., Manetti,R., Vanini,V., Romagnani,P., Maggi,E., & Romagnani,S. (2002) Phenotype, localization, and mechanism of suppression of CD4(+)CD25(+) human thymocytes. J.Exp.Med., 196, 379–387.
Paust,S., Lu,L., McCarty,N., & Cantor,H. (2004) Engagement of B7 on effector T cells by regulatory T cells prevents autoimmune disease. Proc.Natl.Acad.Sci.U.S.A, 101, 10398–10403.
Taylor,P.A., Lees,C.J., Fournier,S., Allison,J.P., Sharpe,A.H., & Blazar,B.R. (2004) B7 expression on T cells down-regulates immune responses through CTLA-4 ligation via T-T interactions [corrections]. J.Immunol., 172, 34–39.
Shevach,E.M. (2002) CD4+ CD25+ suppressor T cells: more questions than answers. Nat.Rev.Immunol., 2, 389–400.
Malek,T.R., Yu,A., Vincek,V., Scibelli,P., & Kong,L. (2002) CD4 regulatory T cells prevent lethal autoimmunity in IL-2Rbeta-deficient mice. Implications for the nonredundant function of IL-2. Immunity., 17, 167–178.
Onizuka,S., Tawara,I., Shimizu,J., Sakaguchi,S., Fujita,T., & Nakayama,E. (1999) Tumor rejection by in vivo administration of anti-CD25 (interleukin-2 receptor alpha) monoclonal antibody. Cancer Res., 59, 3128–3133.
Steitz,J., Bruck,J., Lenz,J., Knop,J., & Tuting,T. (2001) Depletion of CD25(+) CD4(+) T cells and treatment with tyrosinase-related protein 2-transduced dendritic cells enhance the interferon alpha-induced, CD8(+) T-cell-dependent immune defense of B16 melanoma. Cancer Res., 61, 8643–8646.
Nagai,H., Horikawa,T., Hara,I., Fukunaga,A., Oniki,S., Oka,M., Nishigori,C., & Ichihashi,M. (2004) In vivo elimination of CD25+ regulatory T cells leads to tumor rejection of B16F10 melanoma, when combined with interleukin-12 gene transfer. Exp.Dermatol., 13, 613–620.
Prasad,S.J., Farrand,K.J., Matthews,S.A., Chang,J.H., McHugh,R.S., & Ronchese,F. (2005) Dendritic cells loaded with stressed tumor cells elicit long-lasting protective tumor immunity in mice depleted of CD4+CD25+ regulatory T cells. J.Immunol., 174, 90–98.
Dannull,J., Su,Z., Rizzieri,D., Yang,B.K., Coleman,D., Yancey,D., Zhang,A., Dahm,P., Chao,N., Gilboa,E., & Vieweg,J. (2005) Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells. J.Clin.Invest, 115, 3623–3633.
Barnett,B., Kryczek,I., Cheng,P., Zou,W., & Curiel,T.J. (2005) Regulatory T cells in ovarian cancer: biology and therapeutic potential. Am.J.Reprod.Immunol., 54, 369–377.
Antony,P.A., Piccirillo,C.A., Akpinarli,A., Finkelstein,S.E., Speiss,P.J., Surman,D.R., Palmer,D.C., Chan,C.C., Klebanoff,C.A., Overwijk,W.W., Rosenberg,S.A., & Restifo,N.P. (2005) CD8+ T cell immunity against a tumor/self-antigen is augmented by CD4+ T helper cells and hindered by naturally occurring T regulatory cells. J.Immunol., 174, 2591–2601.
Gattinoni,L., Powell,D.J., Jr., Rosenberg,S.A., & Restifo,N.P. (2006) Adoptive immunotherapy for cancer: building on success. Nat.Rev.Immunol., 6, 383–393.
Turk,M.J., Guevara-Patino,J.A., Rizzuto,G.A., Engelhorn,M.E., Sakaguchi,S., & Houghton,A.N. (2004) Concomitant tumor immunity to a poorly immunogenic melanoma is prevented by regulatory T cells. J.Exp.Med., 200, 771–782.
Cohen,A.D., Diab,A., Perales,M.A., Wolchok,J.D., Rizzuto,G., Merghoub,T., Huggins,D., Liu,C., Turk,M.J., Restifo,N.P., Sakaguchi,S., & Houghton,A.N. (2006) Agonist anti-GITR antibody enhances vaccine-induced CD8(+) T-cell responses and tumor immunity. Cancer Res., 66, 4904–4912.
Sugamura,K., Ishii,N., & Weinberg,A.D. (2004) Therapeutic targeting of the effector T-cell co-stimulatory molecule OX40. Nat.Rev.Immunol., 4, 420–431.
Shimizu,J., Yamazaki,S., Takahashi,T., Ishida,Y., & Sakaguchi,S. (2002) Stimulation of CD25(+)CD4(+) regulatory T cells through GITR breaks immunological self-tolerance. Nat.Immunol., 3, 135–142.
Valzasina,B., Guiducci,C., Dislich,H., Killeen,N., Weinberg,A.D., & Colombo,M.P. (2005) Triggering of OX40 (CD134) on CD4(+)CD25+ T cells blocks their inhibitory activity: a novel regulatory role for OX40 and its comparison with GITR. Blood, 105, 2845–2851.
Stephens,G.L., McHugh,R.S., Whitters,M.J., Young,D.A., Luxenberg,D., Carreno,B.M., Collins,M., & Shevach,E.M. (2004) Engagement of glucocorticoid-induced TNFR family-related receptor on effector T cells by its ligand mediates resistance to suppression by CD4+CD25+ T cells. J.Immunol., 173, 5008–5020.
Hodi,F.S. & Dranoff,G. (2006) Combinatorial cancer immunotherapy. Adv.Immunol., 90, 341–368.
Phan,G.Q., Yang,J.C., Sherry,R.M., Hwu,P., Topalian,S.L., Schwartzentruber,D.J., Restifo,N.P., Haworth,L.R., Seipp,C.A., Freezer,L.J., Morton,K.E., Mavroukakis,S.A., Duray,P.H., Steinberg,S.M., Allison,J.P., Davis,T.A., & Rosenberg,S.A. (2003) Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma. Proc.Natl.Acad.Sci.U.S.A, 100, 8372–8377.
Hodi,F.S., Mihm,M.C., Soiffer,R.J., Haluska,F.G., Butler,M., Seiden,M.V., Davis,T., Henry-Spires,R., MacRae,S., Willman,A., Padera,R., Jaklitsch,M.T., Shankar,S., Chen,T.C., Korman,A., Allison,J.P., & Dranoff,G. (2003) Biologic activity of cytotoxic T lymphocyte-associated antigen 4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patients. Proc.Natl.Acad.Sci.U.S.A, 100, 4712–4717.
Attia,P., Phan,G.Q., Maker,A.V., Robinson,M.R., Quezado,M.M., Yang,J.C., Sherry,R.M., Topalian,S.L., Kammula,U.S., Royal,R.E., Restifo,N.P., Haworth,L.R., Levy,C., Mavroukakis,S.A., Nichol,G., Yellin,M.J., & Rosenberg,S.A. (2005) Autoimmunity correlates with tumor regression in patients with metastatic melanoma treated with anti-cytotoxic T-lymphocyte antigen-4. J.Clin.Oncol., 23, 6043–6053.
Sanderson,K., Scotland,R., Lee,P., Liu,D., Groshen,S., Snively,J., Sian,S., Nichol,G., Davis,T., Keler,T., Yellin,M., & Weber,J. (2005) 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, 741–750.
Ribas,A., Camacho,L.H., Lopez-Berestein,G., Pavlov,D., Bulanhagui,C.A., Millham,R., Comin-Anduix,B., Reuben,J.M., Seja,E., Parker,C.A., Sharma,A., Glaspy,J.A., & Gomez-Navarro,J. (2005) 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, 8968–8977.
Beck,K.E., Blansfield,J.A., Tran,K.Q., Feldman,A.L., Hughes,M.S., Royal,R.E., Kammula,U.S., Topalian,S.L., Sherry,R.M., Kleiner,D., Quezado,M., Lowy,I., Yellin,M., Rosenberg,S.A., & Yang,J.C. (2006) Enterocolitis in patients with cancer after antibody blockade of cytotoxic T-lymphocyte-associated antigen 4. J.Clin.Oncol., 24, 2283–2289.
Peggs,K.S., Quezada,S.A., Korman,A.J., & Allison,J.P. (2006) Principles and use of anti-CTLA4 antibody in human cancer immunotherapy. Curr.Opin.Immunol., 18, 206–213.
Lurquin,C., Lethe,B., De Plaen,E., Corbiere,V., Theate,I., van Baren,N., Coulie,P.G., & Boon,T. (2005) Contrasting frequencies of antitumor and anti-vaccine T cells in metastases of a melanoma patient vaccinated with a MAGE tumor antigen. J.Exp.Med., 201, 249–257.
Maker,A.V., Phan,G.Q., Attia,P., Yang,J.C., Sherry,R.M., Topalian,S.L., Kammula,U.S., Royal,R.E., Haworth,L.R., Levy,C., Kleiner,D., Mavroukakis,S.A., Yellin,M., & Rosenberg,S.A. (2005) Tumor regression and autoimmunity in patients treated with cytotoxic T lymphocyte-associated antigen 4 blockade and interleukin 2: a phase I/II study. Ann.Surg.Oncol., 12, 1005–1016.
Atkins,M.B., Lotze,M.T., Dutcher,J.P., Fisher,R.I., Weiss,G., Margolin,K., Abrams,J., Sznol,M., Parkinson,D., Hawkins,M., Paradise,C., Kunkel,L., & Rosenberg,S.A. (1999) High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J.Clin.Oncol., 17, 2105–2116.
Rosenberg,S.A. (2000) Interleukin-2 and the development of immunotherapy for the treatment of patients with cancer. Cancer J.Sci.Am., 6 Suppl 1, S2-S7.
Fong,L., Kavanagh,B., Rini,B.I., Shaw,V., Weinberg,V., & Small,E.J. (2006) A phase I trial of combination immunotherapy with CTLA-4 blockade and GM-CSF in hormone-refractory prostate cancer. Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings, 24, 2508.
Hurwitz,A.A., Sullivan,T.J., Krummel,M.F., Sobel,R.A., & Allison,J.P. (1997) Specific blockade of CTLA-4/B7 interactions results in exacerbated clinical and histologic disease in an actively-induced model of experimental allergic encephalomyelitis. J.Neuroimmunol., 73, 57–62.
Karandikar,N.J., Vanderlugt,C.L., Walunas,T.L., Miller,S.D., & Bluestone,J.A. (1996) CTLA-4: a negative regulator of autoimmune disease. J.Exp.Med., 184, 783–788.
Perrin,P.J., Maldonado,J.H., Davis,T.A., June,C.H., & Racke,M.K. (1996) CTLA-4 blockade enhances clinical disease and cytokine production during experimental allergic encephalomyelitis. J.Immunol., 157, 1333–1336.
Luhder,F., Hoglund,P., Allison,J.P., Benoist,C., & Mathis,D. (1998) Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) regulates the unfolding of autoimmune diabetes. J.Exp.Med., 187, 427–432.
Wang,H.B., Shi,F.D., Li,H., Chambers,B.J., Link,H., & Ljunggren,H.G. (2001) Anti-CTLA-4 antibody treatment triggers determinant spreading and enhances murine myasthenia gravis. J.Immunol., 166, 6430–6436.
Keler,T., Halk,E., Vitale,L., O’Neill,T., Blanset,D., Lee,S., Srinivasan,M., Graziano,R.F., Davis,T., Lonberg,N., & Korman,A. (2003) Activity and safety of CTLA-4 blockade combined with vaccines in cynomolgus macaques. J.Immunol., 171, 6251–6259.
Korman,A., Yellin,M., & Keler,T. (2005) Tumor immunotherapy: preclinical and clinical activity of anti-CTLA4 antibodies. Curr.Opin.Investig.Drugs, 6, 582–591.
Robinson,M.R., Chan,C.C., Yang,J.C., Rubin,B.I., Gracia,G.J., Sen,H.N., Csaky,K.G., & Rosenberg,S.A. (2004) Cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma: a new cause of uveitis. J.Immunother., 27, 478–479.
Blansfield,J.A., Beck,K.E., Tran,K., Yang,J.C., Hughes,M.S., Kammula,U.S., Royal,R.E., Topalian,S.L., Haworth,L.R., Levy,C., Rosenberg,S.A., & Sherry,R.M. (2005) Cytotoxic T-lymphocyte-associated antigen-4 blockage can induce autoimmune hypophysitis in patients with metastatic melanoma and renal cancer. J.Immunother., 28, 593–598.
Dong,H., Strome,S.E., Salomao,D.R., Tamura,H., Hirano,F., Flies,D.B., Roche,P.C., Lu,J., Zhu,G., Tamada,K., Lennon,V.A., Celis,E., & Chen,L. (2002) Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat.Med., 8, 793–800.
Brown,J.A., Dorfman,D.M., Ma,F.R., Sullivan,E.L., Munoz,O., Wood,C.R., Greenfield,E.A., & Freeman,G.J. (2003) Blockade of programmed death-1 ligands on dendritic cells enhances T cell activation and cytokine production. J.Immunol., 170, 1257–1266.
Ohigashi,Y., Sho,M., Yamada,Y., Tsurui,Y., Hamada,K., Ikeda,N., Mizuno,T., Yoriki,R., Kashizuka,H., Yane,K., Tsushima,F., Otsuki,N., Yagita,H., Azuma,M., & Nakajima,Y. (2005) Clinical significance of programmed death-1 ligand-1 and programmed death-1 ligand-2 expression in human esophageal cancer. Clin.Cancer Res., 11, 2947–2953.
Rosenwald,A., Wright,G., Leroy,K., Yu,X., Gaulard,P., Gascoyne,R.D., Chan,W.C., Zhao,T., Haioun,C., Greiner,T.C., Weisenburger,D.D., Lynch,J.C., Vose,J., Armitage,J.O., Smeland,E.B., Kvaloy,S., Holte,H., Delabie,J., Campo,E., Montserrat,E., Lopez-Guillermo,A., Ott,G., Muller-Hermelink,H.K., Connors,J.M., Braziel,R., Grogan,T.M., Fisher,R.I., Miller,T.P., LeBlanc,M., Chiorazzi,M., Zhao,H., Yang,L., Powell,J., Wilson,W.H., Jaffe,E.S., Simon,R., Klausner,R.D., & Staudt,L.M. (2003) Molecular diagnosis of primary mediastinal B cell lymphoma identifies a clinically favorable subgroup of diffuse large B cell lymphoma related to Hodgkin lymphoma. J.Exp.Med., 198, 851–862.
Iwai,Y., Ishida,M., Tanaka,Y., Okazaki,T., Honjo,T., & Minato,N. (2002) 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.U.S.A, 99, 12293–12297.
Strome,S.E., Dong,H., Tamura,H., Voss,S.G., Flies,D.B., Tamada,K., Salomao,D., Cheville,J., Hirano,F., Lin,W., Kasperbauer,J.L., Ballman,K.V., & Chen,L. (2003) B7-H1 blockade augments adoptive T-cell immunotherapy for squamous cell carcinoma. Cancer Res., 63, 6501–6505.
Curiel,T.J., Wei,S., Dong,H., Alvarez,X., Cheng,P., Mottram,P., Krzysiek,R., Knutson,K.L., Daniel,B., Zimmermann,M.C., David,O., Burow,M., Gordon,A., Dhurandhar,N., Myers,L., Berggren,R., Hemminki,A., Alvarez,R.D., Emilie,D., Curiel,D.T., Chen,L., & Zou,W. (2003) Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity. Nat.Med., 9, 562–567.
Carter,L., Fouser,L.A., Jussif,J., Fitz,L., Deng,B., Wood,C.R., Collins,M., Honjo,T., Freeman,G.J., & Carreno,B.M. (2002) PD-1:PD-L inhibitory pathway affects both CD4(+) and CD8(+) T cells and is overcome by IL-2. Eur.J.Immunol., 32, 634–643.
Liu,X., Gao,J.X., Wen,J., Yin,L., Li,O., Zuo,T., Gajewski,T.F., Fu,Y.X., Zheng,P., & Liu,Y. (2003) B7DC/PDL2 promotes tumor immunity by a PD-1-independent mechanism. J.Exp.Med., 197, 1721–1730.
Iwai,Y., Terawaki,S., & Honjo,T. (2005) PD-1 blockade inhibits hematogenous spread of poorly immunogenic tumor cells by enhanced recruitment of effector T cells. Int.Immunol., 17, 133–144.
Suh,W.K., Gajewska,B.U., Okada,H., Gronski,M.A., Bertram,E.M., Dawicki,W., Duncan,G.S., Bukczynski,J., Plyte,S., Elia,A., Wakeham,A., Itie,A., Chung,S., Da Costa,J., Arya,S., Horan,T., Campbell,P., Gaida,K., Ohashi,P.S., Watts,T.H., Yoshinaga,S.K., Bray,M.R., Jordana,M., & Mak,T.W. (2003) The B7 family member B7-H3 preferentially down-regulates T helper type 1-mediated immune responses. Nat.Immunol., 4, 899–906.
Zang,X., Loke,P., Kim,J., Murphy,K., Waitz,R., & Allison,J.P. (2003) B7x: a widely expressed B7 family member that inhibits T cell activation. Proc.Natl.Acad.Sci.U.S.A, 100, 10388–10392.
Prasad,D.V., Richards,S., Mai,X.M., & Dong,C. (2003) B7S1, a novel B7 family member that negatively regulates T cell activation. Immunity., 18, 863–873.
Sica,G.L., Choi,I.H., Zhu,G., Tamada,K., Wang,S.D., Tamura,H., Chapoval,A.I., Flies,D.B., Bajorath,J., & Chen,L. (2003) B7-H4, a molecule of the B7 family, negatively regulates T cell immunity. Immunity., 18, 849–861.
Choi,I.H., Zhu,G., Sica,G.L., Strome,S.E., Cheville,J.C., Lau,J.S., Zhu,Y., Flies,D.B., Tamada,K., & Chen,L. (2003) Genomic organization and expression analysis of B7-H4, an immune inhibitory molecule of the B7 family. J.Immunol., 171, 4650–4654.
Salceda,S., Tang,T., Kmet,M., Munteanu,A., Ghosh,M., Macina,R., Liu,W., Pilkington,G., & Papkoff,J. (2005) The immunomodulatory protein B7-H4 is overexpressed in breast and ovarian cancers and promotes epithelial cell transformation. Exp.Cell Res., 306, 128–141.
Tringler,B., Zhuo,S., Pilkington,G., Torkko,K.C., Singh,M., Lucia,M.S., Heinz,D.E., Papkoff,J., & Shroyer,K.R. (2005) B7-h4 is highly expressed in ductal and lobular breast cancer. Clin.Cancer Res., 11, 1842–1848.
Kryczek,I., Wei,S., Zou,L., Zhu,G., Mottram,P., Xu,H., Chen,L., & Zou,W. (2006a) Cutting Edge: Induction of B7-H4 on APCs through IL-10: Novel Suppressive Mode for Regulatory T Cells. J.Immunol., 177, 40–44.
Kryczek,I., Zou,L., Rodriguez,P., Zhu,G., Wei,S., Mottram,P., Brumlik,M., Cheng,P., Curiel,T., Myers,L., Lackner,A., Alvarez,X., Ochoa,A., Chen,L., & Zou,W. (2006b) B7-H4 expression identifies a novel suppressive macrophage population in human ovarian carcinoma. J.Exp.Med., 203, 871–881.
Han,P., Goularte,O.D., Rufner,K., Wilkinson,B., & Kaye,J. (2004) An inhibitory Ig superfamily protein expressed by lymphocytes and APCs is also an early marker of thymocyte positive selection. J.Immunol., 172, 5931–5939.
Hurchla,M.A., Sedy,J.R., Gavrielli,M., Drake,C.G., Murphy,T.L., & Murphy,K.M. (2005) B and T lymphocyte attenuator exhibits structural and expression polymorphisms and is highly Induced in anergic CD4+ T cells. J.Immunol., 174, 3377–3385.
Sedy,J.R., Gavrieli,M., Potter,K.G., Hurchla,M.A., Lindsley,R.C., Hildner,K., Scheu,S., Pfeffer,K., Ware,C.F., Murphy,T.L., & Murphy,K.M. (2005) B and T lymphocyte attenuator regulates T cell activation through interaction with herpesvirus entry mediator. Nat.Immunol., 6, 90–98.
Gri,G., Gallo,E., Di Carlo,E., Musiani,P., & Colombo,M.P. (2003) OX40 ligand-transduced tumor cell vaccine synergizes with GM-CSF and requires CD40-Apc signaling to boost the host T cell antitumor response. J.Immunol., 170, 99–106.
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Peggs, K.S., Quezada, S.A., Allison, J.P. (2007). Checkpoint Blockade and Combinatorial Immunotherapies. In: Kaufman, H.L., Wolchok, J.D. (eds) General Principles of Tumor Immunotherapy. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-6087-8_16
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