Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Mar;39(13):2835-2843.
doi: 10.1038/s41388-020-1175-x. Epub 2020 Jan 30.

Coordinated Signals From PARP-1 and PARP-2 Are Required to Establish a Proper T Cell Immune Response to Breast Tumors in Mice

Affiliations

Coordinated Signals From PARP-1 and PARP-2 Are Required to Establish a Proper T Cell Immune Response to Breast Tumors in Mice

Lucia Moreno-Lama et al. Oncogene. .

Abstract

Poly(ADP-ribose)-polymerase (PARP)-1 and PARP-2 play an essential role in the DNA damage response. Based on this effect of PARP in the tumor cell itself, PARP inhibitors have emerged as new therapeutic tools both approved and in clinical trials. However, the interactome of multiple other cell types, particularly T cells, within the tumor microenvironment are known to either favor or limit tumorigenesis. Here, we bypassed the embryonic lethality of dually PARP-1/PARP-2-deficient mice by using a PARP-1-deficient mouse with a Cd4-promoter-driven deletion of PARP-2 in T cells to investigate the understudied role of these PARPs in the modulation of T cell responses against AT-3-induced breast tumors. We found that dual PARP-1/PARP-2-deficiency in T cells promotes tumor growth while single deficiency of each protein limited tumor progression. Analysis of tumor-infiltrating cells in dual PARP-1/PARP-2-deficiency host-mice revealed a global change in immunological profile and impaired recruitment and activation of T cells. Conversely, single PARP-1 and PARP-2-deficiency tends to produce an environment with an active and partially upregulated immune response. Our findings pinpoint opposite effects of single and dual PARP-1 and PARP-2-deficiency in modulating the antitumor response with an impact on tumor progression, and will have implications for the development of more selective PARP-centered therapies.

Similar articles

See all similar articles

Cited by 1 article

References

    1. Nat Rev Cancer. 2019 Jul;19(7):392-404 - PubMed

References

    1. Oncoimmunology. 2017 Sep 14;7(1):e1364828 - PubMed

References

    1. Nat Rev Clin Oncol. 2015 Jan;12(1):27-41 - PubMed

References

    1. Cancer Res. 2018 Dec 15;78(24):6717-6725 - PubMed

References

    1. Am J Cancer Res. 2011;1(3):328-346 - PubMed

References

    1. J Immunol. 2007 Sep 1;179(5):2851-9 - PubMed

References

    1. Oncogene. 2010 May 13;29(19):2877-83 - PubMed

References

    1. Cancer Res. 2019 Sep 15;79(18):4557-4566 - PubMed

References

    1. Oncoimmunology. 2015 Jul 1;5(1):e1065370 - PubMed

References

    1. J Biol Chem. 2015 Nov 27;290(48):28675-82 - PubMed

References

    1. Exp Mol Med. 2018 Dec 13;50(12):1-11 - PubMed

References

    1. J Immunol. 2003 May 15;170(10):4881-5 - PubMed

References

    1. Mol Cell. 2015 Jun 18;58(6):911-24 - PubMed

References

    1. Nat Chem Biol. 2018 Feb 14;14(3):236-243 - PubMed

References

    1. Proc Natl Acad Sci U S A. 2006 Oct 3;103(40):14854-9 - PubMed

References

    1. Nat Biotechnol. 2012 Feb 19;30(3):283-8 - PubMed

References

    1. Mol Cell. 2015 Jun 18;58(6):947-58 - PubMed

References

    1. Blood. 2013 Sep 26;122(13):2224-32 - PubMed

References

    1. Nat Rev Clin Oncol. 2018 Sep;15(9):564-576 - PubMed

References

    1. Clin Cancer Res. 2019 Mar 1;25(5):1535-1545 - PubMed

References

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

References

    1. J Natl Cancer Inst. 2015 Feb 03;107(3): - PubMed

References

    1. Cancer Cell. 2014 Nov 10;26(5):638-52 - PubMed

References

    1. BMC Genomics. 2008 Apr 16;9:171 - PubMed

References

    1. Annu Rev Immunol. 2016 May 20;34:539-73 - PubMed

References

    1. Cell Death Differ. 2015 Jul;22(7):1144-57 - PubMed

References

    1. EMBO J. 2003 May 1;22(9):2255-63 - PubMed

References

    1. Nature. 2008 Jul 24;454(7203):436-44 - PubMed

References

    1. Curr Opin Immunol. 2017 Apr;45:43-51 - PubMed

References

    1. Clin Cancer Res. 2015 Nov 15;21(22):5047-56 - PubMed

References

    1. Mol Cell. 2015 Nov 19;60(4):547-60 - PubMed

References

    1. BMC Immunol. 2011 Aug 04;12:43 - PubMed

References

    1. Science. 2016 Jul 1;353(6294):45-50 - PubMed

References

    1. N Engl J Med. 2017 Aug 10;377(6):523-533 - PubMed

References

    1. Mol Immunol. 2008 Apr;45(7):1863-71 - PubMed

References

    1. J Exp Med. 2012 Jun 4;209(6):1201-17 - PubMed

References

    1. Sci Rep. 2017 Feb 09;7:41962 - PubMed

References

    1. Cancer Res. 2013 Jan 1;73(1):128-38 - PubMed

References

    1. EMBO J. 2006 Sep 20;25(18):4350-60 - PubMed

References

    1. Blood. 2013 Jul 4;122(1):44-54 - PubMed

LinkOut - more resources

Feedback