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Mechanism of tumor rejection with doublets of CTLA-4, PD-1/PD-L1, or IDO blockade involves restored IL-2 production and proliferation of CD8(+) T cells directly within the tumor microenvironment.

Spranger S, Koblish HK, Horton B, Scherle PA, Newton R, Gajewski TF.

J Immunother Cancer. 2014 Feb 18;2:3. doi: 10.1186/2051-1426-2-3. eCollection 2014.


PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors.

Curran MA, Montalvo W, Yagita H, Allison JP.

Proc Natl Acad Sci U S A. 2010 Mar 2;107(9):4275-80. doi: 10.1073/pnas.0915174107. Epub 2010 Feb 16.


Indoleamine 2,3-dioxygenase is a critical resistance mechanism in antitumor T cell immunotherapy targeting CTLA-4.

Holmgaard RB, Zamarin D, Munn DH, Wolchok JD, Allison JP.

J Exp Med. 2013 Jul 1;210(7):1389-402. doi: 10.1084/jem.20130066. Epub 2013 Jun 10.


Dual blockade of PD-1 and CTLA-4 combined with tumor vaccine effectively restores T-cell rejection function in tumors.

Duraiswamy J, Kaluza KM, Freeman GJ, Coukos G.

Cancer Res. 2013 Jun 15;73(12):3591-603. doi: 10.1158/0008-5472.CAN-12-4100. Epub 2013 Apr 30.


PD-L1/B7H-1 inhibits the effector phase of tumor rejection by T cell receptor (TCR) transgenic CD8+ T cells.

Blank C, Brown I, Peterson AC, Spiotto M, Iwai Y, Honjo T, Gajewski TF.

Cancer Res. 2004 Feb 1;64(3):1140-5.


Anti-PD-1 antibody significantly increases therapeutic efficacy of Listeria monocytogenes (Lm)-LLO immunotherapy.

Mkrtichyan M, Chong N, Abu Eid R, Wallecha A, Singh R, Rothman J, Khleif SN.

J Immunother Cancer. 2013 Aug 29;1:15. doi: 10.1186/2051-1426-1-15. eCollection 2013.


Combination CTLA-4 blockade and 4-1BB activation enhances tumor rejection by increasing T-cell infiltration, proliferation, and cytokine production.

Curran MA, Kim M, Montalvo W, Al-Shamkhani A, Allison JP.

PLoS One. 2011 Apr 29;6(4):e19499. doi: 10.1371/journal.pone.0019499.


Glioblastoma Eradication Following Immune Checkpoint Blockade in an Orthotopic, Immunocompetent Model.

Reardon DA, Gokhale PC, Klein SR, Ligon KL, Rodig SJ, Ramkissoon SH, Jones KL, Conway AS, Liao X, Zhou J, Wen PY, Van Den Abbeele AD, Hodi FS, Qin L, Kohl NE, Sharpe AH, Dranoff G, Freeman GJ.

Cancer Immunol Res. 2016 Feb;4(2):124-35. doi: 10.1158/2326-6066.CIR-15-0151. Epub 2015 Nov 6.


Simultaneous inhibition of two regulatory T-cell subsets enhanced Interleukin-15 efficacy in a prostate tumor model.

Yu P, Steel JC, Zhang M, Morris JC, Waitz R, Fasso M, Allison JP, Waldmann TA.

Proc Natl Acad Sci U S A. 2012 Apr 17;109(16):6187-92. doi: 10.1073/pnas.1203479109. Epub 2012 Apr 2.


Combined Trabectedin and anti-PD1 antibody produces a synergistic antitumor effect in a murine model of ovarian cancer.

Guo Z, Wang H, Meng F, Li J, Zhang S.

J Transl Med. 2015 Jul 29;13:247. doi: 10.1186/s12967-015-0613-y.


PD-1 blockade and OX40 triggering synergistically protects against tumor growth in a murine model of ovarian cancer.

Guo Z, Wang X, Cheng D, Xia Z, Luan M, Zhang S.

PLoS One. 2014 Feb 27;9(2):e89350. doi: 10.1371/journal.pone.0089350. eCollection 2014.


Immunotherapy: Beyond Anti-PD-1 and Anti-PD-L1 Therapies.

Antonia SJ, Vansteenkiste JF, Moon E.

Am Soc Clin Oncol Educ Book. 2016;35:e450-8. doi: 10.14694/EDBK_158712. Review.


Characterization of the in vivo immune network of IDO, tryptophan metabolism, PD-L1, and CTLA-4 in circulating immune cells in melanoma.

Chevolet I, Speeckaert R, Schreuer M, Neyns B, Krysko O, Bachert C, Hennart B, Allorge D, van Geel N, Van Gele M, Brochez L.

Oncoimmunology. 2015 Apr 2;4(3):e982382. eCollection 2015 Mar.


Combined PD-1 blockade and GITR triggering induce a potent antitumor immunity in murine cancer models and synergizes with chemotherapeutic drugs.

Lu L, Xu X, Zhang B, Zhang R, Ji H, Wang X.

J Transl Med. 2014 Feb 7;12:36. doi: 10.1186/1479-5876-12-36.


Immune checkpoint proteins: a new therapeutic paradigm for cancer--preclinical background: CTLA-4 and PD-1 blockade.

Weber J.

Semin Oncol. 2010 Oct;37(5):430-9. doi: 10.1053/j.seminoncol.2010.09.005. Review.


The Next Immune-Checkpoint Inhibitors: PD-1/PD-L1 Blockade in Melanoma.

Mahoney KM, Freeman GJ, McDermott DF.

Clin Ther. 2015 Apr 1;37(4):764-82. doi: 10.1016/j.clinthera.2015.02.018. Epub 2015 Mar 29. Review.


Targeting CD73 enhances the antitumor activity of anti-PD-1 and anti-CTLA-4 mAbs.

Allard B, Pommey S, Smyth MJ, Stagg J.

Clin Cancer Res. 2013 Oct 15;19(20):5626-35. doi: 10.1158/1078-0432.CCR-13-0545. Epub 2013 Aug 27.


Simultaneous blockade of multiple immune system inhibitory checkpoints enhances antitumor activity mediated by interleukin-15 in a murine metastatic colon carcinoma model.

Yu P, Steel JC, Zhang M, Morris JC, Waldmann TA.

Clin Cancer Res. 2010 Dec 15;16(24):6019-28. doi: 10.1158/1078-0432.CCR-10-1966. Epub 2010 Oct 5.


Durable therapeutic efficacy utilizing combinatorial blockade against IDO, CTLA-4, and PD-L1 in mice with brain tumors.

Wainwright DA, Chang AL, Dey M, Balyasnikova IV, Kim CK, Tobias A, Cheng Y, Kim JW, Qiao J, Zhang L, Han Y, Lesniak MS.

Clin Cancer Res. 2014 Oct 15;20(20):5290-301. doi: 10.1158/1078-0432.CCR-14-0514. Epub 2014 Apr 1. Erratum in: Clin Cancer Res. 2015 Feb 1;21(3):662.


Therapeutic uses of anti-PD-1 and anti-PD-L1 antibodies.

Philips GK, Atkins M.

Int Immunol. 2015 Jan;27(1):39-46. doi: 10.1093/intimm/dxu095. Epub 2014 Oct 16. Review.


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