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Review
, 145 (12), 3021-3036

Preclinical Rationale and Clinical Efficacy of Antiangiogenic Therapy and Immune Checkpoint Blockade Combination Therapy in Urogenital Tumors

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Review

Preclinical Rationale and Clinical Efficacy of Antiangiogenic Therapy and Immune Checkpoint Blockade Combination Therapy in Urogenital Tumors

Ning Zhu et al. J Cancer Res Clin Oncol.

Abstract

Purpose: In recent years, immune checkpoint blockade (ICB) therapies have shown good clinical responses in various solid cancers. However, a major challenge in the process of ICB treatment is when tumors do not have enough infiltrating T cells. Antiangiogenic drugs targeting vascular endothelial growth factor (VEGF) and its receptors have been approved for the treatment of various malignant solid tumors alone or in combination with other therapies. Our review mainly discusses the preclinical rationale and clinical efficacy of antiangiogenic and ICB combination therapy in urogenital tumors.

Methods: We reviewed relevant literature on preclinical research and clinical trial results regarding antiangiogenic and ICB combination therapy in urogenital tumors from PubMed. In addition, we searched ongoing clinical trials on ClinicalTrials.gov to collect information related to this specific topic.

Results: Antiangiogenesis therapy could enhance T cell recruitment and increase T cell infiltration into the tumor microenvironment by blocking VEGF-VEGF receptor 2 binding and downstream signaling pathways to normalize tumor blood vessels. The combination of ICB and antiangiogenesis therapy could improve antitumor activity according to subsequent preclinical experiments and several phase I/II/III clinical trials on urogenital tumors.

Conclusion: Combined therapy has shown some antitumor efficacy in several urogenital tumors, such as metastatic renal cell carcinoma, metastatic urothelial and genitourinary tumors, endometrial carcinoma, ovarian cancer, and fallopian tube cancer. Combination therapy is a promising strategy that can be used to improve the therapeutic efficacy, and the identification of precise biomarkers of this combined therapy is the direction of future studies.

Keywords: PD-1; PD-L1; T cell infiltration; Tumor blood vessel; Urogenital tumor; VEGF.

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References

    1. Immunity. 2002 Jan;16(1):23-35 - PubMed

References

    1. J Immunol. 1999 May 15;162(10):5813-20 - PubMed

References

    1. Lancet Oncol. 2015 Nov;16(15):1473-1482 - PubMed

References

    1. Cancer Metastasis Rev. 2011 Mar;30(1):83-95 - PubMed

References

    1. Cancer Cell. 2015 Apr 13;27(4):450-61 - PubMed

References

    1. N Engl J Med. 2015 Nov 5;373(19):1814-23 - PubMed

References

    1. Lancet Oncol. 2018 Apr;19(4):451-460 - PubMed

References

    1. N Engl J Med. 2015 Nov 5;373(19):1803-13 - PubMed

References

    1. Nat Rev Cancer. 2012 Mar 22;12(4):237-51 - PubMed

References

    1. Curr Opin Genet Dev. 2011 Feb;21(1):73-9 - PubMed

References

    1. Immunity. 1994 Dec;1(9):793-801 - PubMed

References

    1. J Hematol Oncol. 2017 Jan 25;10(1):34 - PubMed

References

    1. Nat Rev Immunol. 2018 Mar;18(3):195-203 - PubMed

References

    1. Lancet Oncol. 2009 Jan;10(1):25-34 - PubMed

References

    1. Cancer Immunol Immunother. 2017 May;66(5):551-564 - PubMed

References

    1. Clin Cancer Res. 2007 Mar 15;13(6):1757-61 - PubMed

References

    1. Dev Cell. 2016 Apr 18;37(2):114-25 - PubMed

References

    1. Cancer Res. 2015 Jun 1;75(11):2139-45 - PubMed

References

    1. Oncology (Williston Park). 2016 Jan;30(1):59-66, 69 - PubMed

References

    1. J Immunother Cancer. 2018 Nov 6;6(Suppl 1):114 - PubMed

References

    1. J Intern Med. 2013 Feb;273(2):114-27 - PubMed

References

    1. Cancer Cell. 2004 Dec;6(6):553-63 - PubMed

References

    1. N Engl J Med. 2010 Aug 19;363(8):711-23 - PubMed

References

    1. Science. 1993 May 28;260(5112):1317-20 - PubMed

References

    1. J Immunother Cancer. 2018 Oct 22;6(1):109 - PubMed

References

    1. J Clin Oncol. 2013 Jun 10;31(17):2205-18 - PubMed

References

    1. Nat Rev Immunol. 2018 Aug;18(8):485-497 - PubMed

References

    1. J Clin Oncol. 2012 Jul 1;30(19):2401-7 - PubMed

References

    1. Ther Adv Med Oncol. 2013 Mar;5(2):133-41 - PubMed

References

    1. Curr Opin Immunol. 2015 Apr;33:55-63 - PubMed

References

    1. Mol Cancer Ther. 2011 May;10(5):770-83 - PubMed

References

    1. Annu Rev Biomed Eng. 2014 Jul 11;16:321-46 - PubMed

References

    1. Cancer Metastasis Rev. 2007 Jun;26(2):281-90 - PubMed

References

    1. Nature. 1993 Nov 4;366(6450):76-9 - PubMed

References

    1. J Clin Oncol. 2012 Jan 10;30(2):134-41 - PubMed

References

    1. Lancet. 2014 Jan 4;383(9911):31-39 - PubMed

References

    1. Proc Natl Acad Sci U S A. 2004 Dec 7;101(49):17174-9 - PubMed

References

    1. Cancer Cell. 2018 Apr 9;33(4):649-663.e4 - PubMed

References

    1. Lancet. 2013 Jan 26;381(9863):303-12 - PubMed

References

    1. Proc Natl Acad Sci U S A. 1990 Jul;87(13):5031-5 - PubMed

References

    1. J Clin Oncol. 2017 Jul 1;35(19):2193-2202 - PubMed

References

    1. Nat Med. 2014 Jun;20(6):607-15 - PubMed

References

    1. Immunity. 1994 Aug;1(5):405-13 - PubMed

References

    1. Nat Med. 2001 Sep;7(9):987-9 - PubMed

References

    1. J Exp Med. 1971 Feb 1;133(2):275-88 - PubMed

References

    1. J Exp Med. 2000 Oct 2;192(7):1027-34 - PubMed

References

    1. N Engl J Med. 2014 May 1;370(18):1769-70 - PubMed

References

    1. J Clin Oncol. 2011 Jul 1;29(19):2660-6 - PubMed

References

    1. N Engl J Med. 2019 Mar 21;380(12):1116-1127 - PubMed

References

    1. Angiogenesis. 2017 May;20(2):185-204 - PubMed

References

    1. Nat Med. 1996 Sep;2(9):992-7 - PubMed

References

    1. Cancer Cell. 2014 Nov 10;26(5):605-22 - PubMed

References

    1. Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8372-7 - PubMed

References

    1. Nat Rev Cancer. 2008 Aug;8(8):592-603 - PubMed

References

    1. J Clin Oncol. 2013 Oct 10;31(29):3639-46 - PubMed

References

    1. Cancer Discov. 2018 Sep;8(9):1069-1086 - PubMed

References

    1. Science. 2017 Mar 31;355(6332):1428-1433 - PubMed

References

    1. Cancer Control. 2014 Jul;21(3):231-7 - PubMed

References

    1. Annu Rev Immunol. 2001;19:565-94 - PubMed

References

    1. Nature. 2014 Nov 27;515(7528):563-7 - PubMed

References

    1. Science. 1993 Nov 5;262(5135):905-7 - PubMed

References

    1. Nature. 2017 Apr 13;544(7649):250-254 - PubMed

References

    1. Nat Rev Cancer. 2002 Oct;2(10):795-803 - PubMed

References

    1. Expert Opin Investig Drugs. 2016;25(5):597-611 - PubMed

References

    1. Ann Oncol. 2016 Mar;27(3):409-16 - PubMed

References

    1. Clin Cancer Res. 2019 Jan 15;25(2):515-523 - PubMed

References

    1. Immunity. 2002 Aug;17(2):201-10 - PubMed

References

    1. Lancet. 2016 Jul 30;388(10043):518-29 - PubMed

References

    1. Lancet. 2017 Jan 7;389(10064):56-66 - PubMed

References

    1. Nature. 2013 Jul 4;499(7456):43-9 - PubMed

References

    1. Lancet. 2014 Jul 26;384(9940):319-28 - PubMed

References

    1. Science. 1993 Nov 5;262(5135):909-11 - PubMed

References

    1. Lancet. 2014 Aug 23;384(9944):665-73 - PubMed

References

    1. J Exp Med. 1998 Jul 6;188(1):205-10 - PubMed

References

    1. Cancer Cell. 2005 Oct;8(4):299-309 - PubMed

References

    1. Nat Immunol. 2002 Jul;3(7):611-8 - PubMed

References

    1. N Engl J Med. 2019 Mar 21;380(12):1103-1115 - PubMed

References

    1. Cancer Immunol Immunother. 2005 Apr;54(4):307-14 - PubMed

References

    1. J Immunol. 2004 Jul 15;173(2):945-54 - PubMed

References

    1. Lancet. 2013 Jan 26;381(9863):295-302 - PubMed

References

    1. Cancer Metastasis Rev. 1996 Jun;15(2):195-204 - PubMed

References

    1. Ann Oncol. 2016 Sep;27(suppl 5):v58-v68 - PubMed

References

    1. Lancet Oncol. 2014 Oct;15(11):1224-35 - PubMed

References

    1. Immunol Rev. 2010 Jul;236:219-42 - PubMed

References

    1. Proc Natl Acad Sci U S A. 2015 Nov 17;112(46):14325-30 - PubMed

References

    1. Nat Med. 2003 Jun;9(6):669-76 - PubMed

References

    1. Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3360-5 - PubMed

References

    1. N Engl J Med. 2017 Mar 16;376(11):1015-1026 - PubMed

References

    1. Cell. 2000 Jan 7;100(1):57-70 - PubMed

References

    1. Immunity. 2013 Jul 25;39(1):1-10 - PubMed

References

    1. Cancer Res. 2014 Feb 1;74(3):665-74 - PubMed

References

    1. Ann Oncol. 2014 Nov;25(11):2178-84 - PubMed

References

    1. Front Immunol. 2016 Dec 20;7:621 - PubMed

References

    1. Nat Rev Immunol. 2018 Aug;18(8):527-535 - PubMed

References

    1. Nat Immunol. 2001 Jan;2(1):37-44 - PubMed

References

    1. Lancet Oncol. 2010 Oct;11(10):962-72 - PubMed

References

    1. Cancer Res. 2006 Apr 1;66(7):3381-5 - PubMed

References

    1. J Hematol Oncol. 2017 Aug 3;10(1):146 - PubMed

References

    1. Biochem Biophys Res Commun. 2005 Jul 29;333(2):328-35 - PubMed

References

    1. J Exp Med. 1991 Sep 1;174(3):561-9 - PubMed

References

    1. Lancet. 2011 Dec 3;378(9807):1931-9 - PubMed

References

    1. Nat Genet. 1994 May;7(1):85-90 - PubMed

References

    1. Clin Cancer Res. 2007 Jan 15;13(2 Pt 2):671s-679s - PubMed

References

    1. Science. 2018 Mar 23;359(6382):1350-1355 - PubMed

References

    1. Nat Med. 2018 Jun;24(6):749-757 - PubMed

References

    1. Nat Immunol. 2001 Mar;2(3):261-8 - PubMed

References

    1. J Immunol. 2006 Oct 1;177(7):4376-83 - PubMed

References

    1. J Exp Med. 2009 Dec 21;206(13):3015-29 - PubMed

References

    1. Clin Cancer Res. 2011 Nov 15;17(22):6958-62 - PubMed

References

    1. Nat Rev Cancer. 2003 Jun;3(6):401-10 - PubMed

References

    1. Eur Urol. 2015 May;67(5):913-24 - PubMed

References

    1. J Exp Med. 1997 Feb 3;185(3):393-403 - PubMed

References

    1. J Immunol. 2000 May 15;164(10):5319-27 - PubMed

References

    1. Science. 2011 Apr 29;332(6029):600-3 - PubMed

References

    1. Nature. 2005 Dec 15;438(7070):967-74 - PubMed

References

    1. Nature. 1994 May 26;369(6478):327-9 - PubMed

References

    1. J Exp Med. 2015 Feb 9;212(2):139-48 - PubMed

References

    1. J Exp Med. 2009 Feb 16;206(2):421-34 - PubMed

References

    1. Lancet Oncol. 2013 Oct;14(11):1035-1037 - PubMed

References

    1. Cell. 2017 Nov 30;171(6):1301-1315.e14 - PubMed

References

    1. Cancer Immunol Res. 2014 Jul;2(7):632-42 - PubMed

References

    1. Cancer Immun. 2013;13:5 - PubMed

References

    1. Lancet Oncol. 2018 Mar;19(3):405-415 - PubMed

References

    1. Cancer Res. 1999 Aug 1;59(15):3776-82 - PubMed

References

    1. Curr Opin Immunol. 2012 Apr;24(2):207-12 - PubMed

References

    1. Cancer Res. 2018 Aug 1;78(15):4270-4281 - PubMed

References

    1. Nat Rev Immunol. 2012 Mar 22;12(4):253-68 - PubMed

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