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      PARP inhibition generates enhanced CD8+ central memory T cells by transcriptional and metabolic reprogramming – Immunology Research


    • Klebanoff, C. A. et al. Determinants of successful CD8+ T-cell adoptive immunotherapy for large established tumors in mice. Clin. Cancer Res. 17, 5343–5352 (2011).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Verma, V. et al. MEK inhibition reprograms CD8+ T lymphocytes into memory stem cells with potent antitumor effects. Nat. Immunol. 22, 53–66 (2021).

      Article 
      PubMed 

      Google Scholar
       

    • Zhou, C. et al. High density of intratumor CD45RO+ memory tumor-infiltrating lymphocytes predicts favorable prognosis in patients with oral squamous cell carcinoma. J. Oral Maxillofac. Surg. 77, 536–545 (2019).

      Article 
      PubMed 

      Google Scholar
       

    • Klebanoff, C. A. et al. Central memory self/tumor-reactive CD8+ T cells confer superior antitumor immunity compared with effector memory T cells. Proc. Natl Acad. Sci. USA 102, 9571–9576 (2005).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Klebanoff, C. A., Gattinoni, L. & Restifo, N. P. CD8+ T-cell memory in tumor immunology and immunotherapy. Immunol. Rev. 211, 214–224 (2006).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Busch, D. H., Frassle, S. P., Sommermeyer, D., Buchholz, V. R. & Riddell, S. R. Role of memory T cell subsets for adoptive immunotherapy. Semin. Immunol. 28, 28–34 (2016).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Offringa, R., Kotzner, L., Huck, B. & Urbahns, K. The expanding role for small molecules in immuno-oncology. Nat. Rev. Drug Discov. 21, 821–840 (2022).

      Article 
      PubMed 

      Google Scholar
       

    • Lord, C. J. & Ashworth, A. PARP inhibitors: synthetic lethality in the clinic. Science 355, 1152–1158 (2017).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Murai, J. et al. Trapping of PARP1 and PARP2 by clinical PARP inhibitors. Cancer Res. 72, 5588–5599 (2012).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Sonnenblick, A., de Azambuja, E., Azim, H. A. Jr. & Piccart, M. An update on PARP inhibitors–moving to the adjuvant setting. Nat. Rev. Clin. Oncol. 12, 27–41 (2015).

      Article 
      PubMed 

      Google Scholar
       

    • Kim, D. & Nam, H. J. PARP inhibitors: clinical limitations and recent attempts to overcome them. Int. J. Mol. Sci. https://doi.org/10.3390/ijms23158412 (2022).

    • Yelamos, J. et al. PARP-2 deficiency affects the survival of CD4+CD8+ double-positive thymocytes. EMBO J. 25, 4350–4360 (2006).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Saenz, L. et al. Transcriptional regulation by poly(ADP-ribose) polymerase-1 during T cell activation. BMC Genomics 9, 171 (2008).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Valdor, R. et al. Regulation of NFAT by poly(ADP-ribose) polymerase activity in T cells. Mol. Immunol. 45, 1863–1871 (2008).

      Article 
      PubMed 

      Google Scholar
       

    • Pantelidou, C. et al. PARP inhibitor efficacy depends on CD8+ T-cell recruitment via intratumoral STING pathway activation in BRCA-deficient models of triple-negative breast cancer. Cancer Discov. 9, 722–737 (2019).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Shen, J. et al. PARPi triggers the STING-dependent immune response and enhances the therapeutic efficacy of immune checkpoint blockade independent of BRCAness. Cancer Res. 79, 311–319 (2019).

      Article 
      PubMed 

      Google Scholar
       

    • Bustos, M. A. et al. MiR-181a targets STING to drive PARP inhibitor resistance in BRCA- mutated triple-negative breast cancer and ovarian cancer. Cell Biosci. 13, 200 (2023).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Staniszewska, A. D. et al. PARP inhibition is a modulator of anti-tumor immune response in BRCA-deficient tumors. Oncoimmunology 11, 2083755 (2022).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Sun, R. et al. Olaparib suppresses MDSC recruitment via SDF1α/CXCR4 axis to improve the anti-tumor efficacy of CAR-T cells on breast cancer in mice. Mol. Ther. 29, 60–74 (2021).

      Article 
      PubMed 

      Google Scholar
       

    • Luo, L. & Keyomarsi, K. PARP inhibitors as single agents and in combination therapy: the most promising treatment strategies in clinical trials for BRCA-mutant ovarian and triple-negative breast cancers. Expert Opin. Investig. Drugs 31, 607–631 (2022).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Kretschmer, L. et al. Differential expansion of T central memory precursor and effector subsets is regulated by division speed. Nat. Commun. 11, 113 (2020).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Choi, H., Song, H. & Jung, Y. W. The roles of CCR7 for the homing of memory CD8+ T cells into their survival niches. Immune Netw. 20, e20 (2020).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Barski, A. et al. Rapid recall ability of memory T cells is encoded in their epigenome. Sci. Rep. 7, 39785 (2017).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Zhang, L. & Romero, P. Metabolic control of CD8+ T cell fate decisions and antitumor immunity. Trends Mol. Med. 24, 30–48 (2018).

      Article 
      PubMed 

      Google Scholar
       

    • Austin, S. & St-Pierre, J. PGC1α and mitochondrial metabolism–emerging concepts and relevance in ageing and neurodegenerative disorders. J. Cell Sci. 125, 4963–4971 (2012).

      Article 
      PubMed 

      Google Scholar
       

    • Krishnakumar, R. & Kraus, W. L. The PARP side of the nucleus: molecular actions, physiological outcomes, and clinical targets. Mol Cell 39, 8–24 (2010).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Kraus, W. L. & Lis, J. T. PARP goes transcription. Cell 113, 677–683 (2003).

      Article 
      PubMed 

      Google Scholar
       

    • Illuzzi, G. et al. Preclinical characterization of AZD5305, a next-generation, highly selective PARP1 inhibitor and trapper. Clin. Cancer Res. 28, 4724–4736 (2022).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Kraus, W. L. & Hottiger, M. O. PARP-1 and gene regulation: progress and puzzles. Mol. Aspects Med. 34, 1109–1123 (2013).

      Article 
      PubMed 

      Google Scholar
       

    • Pietrzak, J., Gronkowska, K. & Robaszkiewicz, A. PARP traps rescue the pro-inflammatory response of human macrophages in the in vitro model of LPS-induced tolerance. Pharmaceuticals 14, 170 (2021).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Dutto, I., Tillhon, M., Cazzalini, O., Stivala, L. A. & Prosperi, E. Biology of the cell cycle inhibitor p21(CDKN1A): molecular mechanisms and relevance in chemical toxicology. Arch. Toxicol. 89, 155–178 (2015).

      Article 
      PubMed 

      Google Scholar
       

    • Delpoux, A., Lai, C. Y., Hedrick, S. M. & Doedens, A. L. FOXO1 opposition of CD8+ T cell effector programming confers early memory properties and phenotypic diversity. Proc. Natl Acad. Sci. USA 114, E8865–E8874 (2017).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Gray, S. M., Amezquita, R. A., Guan, T., Kleinstein, S. H. & Kaech, S. M. Polycomb repressive complex 2-mediated chromatin repression guides effector CD8+ T cell terminal differentiation and loss of multipotency. Immunity 46, 596–608 (2017).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Ouyang, W., Beckett, O., Flavell, R. A. & Li, M. O. An essential role of the Forkhead-box transcription factor Foxo1 in control of T cell homeostasis and tolerance. Immunity 30, 358–371 (2009).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Chung, H. T. & Joe, Y. Antagonistic crosstalk between SIRT1, PARP-1, and -2 in the regulation of chronic inflammation associated with aging and metabolic diseases. Integr. Med. Res. 3, 198–203 (2014).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Matsuzaki, H. et al. Acetylation of Foxo1 alters its DNA-binding ability and sensitivity to phosphorylation. Proc. Natl Acad. Sci. USA 102, 11278–11283 (2005).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Chan, J. D. et al. FOXO1 enhances CAR T cell stemness, metabolic fitness and efficacy. Nature 629, 201–210 (2024).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Doan, A. E. et al. FOXO1 is a master regulator of memory programming in CAR T cells. Nature 629, 211–218 (2024).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Cruz-Bermudez, A. et al. Cisplatin resistance involves a metabolic reprogramming through ROS and PGC-1α in NSCLC which can be overcome by OXPHOS inhibition. Free Radic. Biol. Med. 135, 167–181 (2019).

      Article 
      PubMed 

      Google Scholar
       

    • Mehta, A. K. et al. Targeting immunosuppressive macrophages overcomes PARP inhibitor resistance in BRCA1-associated triple-negative breast cancer. Nat. Cancer 2, 66–82 (2021).

      Article 
      PubMed 

      Google Scholar
       

    • Jeng, M. Y. et al. Metabolic reprogramming of human CD8+ memory T cells through loss of SIRT1. J. Exp. Med. 215, 51–62 (2018).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Chatterjee, N. & Walker, G. C. Mechanisms of DNA damage, repair, and mutagenesis. Environ. Mol. Mutagen. 58, 235–263 (2017).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Cecchini, M. et al. Quantitative DNA repair biomarkers and immune profiling for temozolomide and olaparib in metastatic colorectal cancer. Cancer Res. Commun. 3, 1132–1139 (2023).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Lampert, E. J. et al. Combination of PARP inhibitor olaparib, and PD-L1 inhibitor durvalumab, in recurrent ovarian cancer: a proof-of-concept phase II study. Clin. Cancer Res. 26, 4268–4279 (2020).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Ji, Y. et al. Identification of the genomic insertion site of Pmel-1 TCR alpha and beta transgenes by next-generation sequencing. PLoS ONE 9, e96650 (2014).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Lin, K. Y. et al. Treatment of established tumors with a novel vaccine that enhances major histocompatibility class II presentation of tumor antigen. Cancer Res. 56, 21–26 (1996).

      PubMed 

      Google Scholar
       

    • Sukumar, M. et al. Mitochondrial membrane potential identifies cells with enhanced stemness for cellular therapy. Cell Metab. 23, 63–76 (2016).

      Article 
      PubMed 

      Google Scholar
       

    • Verma, V. et al. PD-1 blockade in subprimed CD8 cells induces dysfunctional PD-1+CD38hi cells and anti-PD-1 resistance. Nat. Immunol. 20, 1231–1243 (2019).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Shrimali, R. K. et al. Concurrent PD-1 blockade negates the effects of OX40 agonist antibody in combination immunotherapy through inducing T-cell apoptosis. Cancer Immunol. Res. 5, 755–766 (2017).

      Article 
      PubMed 

      Google Scholar
       

    • Nandre, R. et al. IDO vaccine ablates immune-suppressive myeloid populations and enhances antitumor effects independent of tumor cell IDO status. Cancer Immunol. Res. 10, 571–580 (2022).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       



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