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PARP7 and nucleic acid-driven oncosuppression

Cellular & Molecular Immunology volume 21, pages 1177–1179 (2024)Cite this article

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TCDD-inducible poly(ADP-ribose) polymerase (TIPARP, best known as PARP7) has previously been shown to promote oncogenesis by limiting the cytosolic accumulation of potentially interferogenic nucleic acids in malignant cells or the precursors thereof. Recent data indicate that the oncogenic activity of PARP7 is derived at least partially from its ability to suppress apoptotic cell death upon mono-ADP-ribosylation of FOS-like 1, AP-1 transcription factor subunit (FOSL1, best known as FRA1) [1].

The natural and therapy-driven control of malignant lesions by the host immune system (i.e., immunosurveillance) ultimately relies on the activation of adaptive, tumor-specific immunity, with a prominent role for type I interferon (IFN) signaling originating from neoplastic (and non-neoplastic) components of the tumor microenvironment [2, 3]. PARP7 is a poorly investigated member of the poly(ADP-ribose) polymerase (PARP) protein family that has been shown to suppress type I IFN signaling in malignant cells by ensuring proficient DNA repair and hence limiting the cytosolic accumulation of potentially interferogenic nucleic acids [4]. Similar to several other proteins involved in DNA repair, PARP family members play a major role in the maintenance of genomic integrity during exposure to stress, including oncogenic stress, de facto preventing the initiation of (generally) unwarranted inflammatory responses [5]. Recent data have demonstrated that in addition to suppressing type I IFN responses in malignant cells, PARP7 restricts the activation of cancer cell-intrinsic oncosuppressive programs orchestrated by interferon regulatory factor 1 (IRF1) and IRF3 that culminate in caspase 8 (CASP8) activation and apoptotic cell death [1].

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Acknowledgements

The LG lab is/has been supported (as a PI, unless otherwise indicated) by one NIH R01 grant (#CA271915), by two Breakthrough Level 2 grants from the US DoD BCRP (#BC180476P1, #BC210945); by a grant from the STARR Cancer Consortium (#I16-0064), by a Transformative Breast Cancer Consortium Grant from the US DoD BCRP (#W81XWH2120034, PI: Formenti), by a U54 grant from NIH/NCI (#CA274291, PIs: Deasy, Formenti, Weichselbaum); by the 2019 Laura Ziskin Prize in Translational Research (#ZP-6177, PI: Formenti) from the Stand Up to Cancer (SU2C) Foundation, by a Mantle Cell Lymphoma Research Initiative (MCL-RI, PI: Chen-Kiang) grant from the Leukemia and Lymphoma Society (LLS), by a Rapid Response Grant from the Functional Genomics Initiative (New York, US), by a pre-SPORE grant (PIs: Demaria, Formenti), a Collaborative Research Initiative Grant and a Clinical Trials Innovation Grant from the Sandra and Edward Meyer Cancer Center (New York, US), by startup funds from the Dept. of Radiation Oncology at Weill Cornell Medicine (New York, US), and by industrial collaborations with Lytix Biopharma (Oslo, Norway), Promontory (New York, US) and Onxeo (Paris, France) as well as by donations from Promontory (New York, US), the Luke Heller TECPR2 Foundation (Boston, US), Sotio a.s. (Prague, Czech Republic), Lytix Biopharma (Oslo, Norway), Onxeo (Paris, France), Ricerchiamo (Brescia, Italy), and Noxopharm (Chatswood, Australia).

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Authors and Affiliations

  1. Department of Radiation Oncology, Weill Cornell Medicine, New York, NY, USA

    Flavie Naulin, Emma Guilbaud & Lorenzo Galluzzi

  2. Sandra and Edward Meyer Cancer Center, New York, NY, USA

    Lorenzo Galluzzi

  3. Caryl and Israel Englander Institute for Precision Medicine, New York, NY, USA

    Lorenzo Galluzzi

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  1. Flavie Naulin
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  2. Emma Guilbaud
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  3. Lorenzo Galluzzi
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Contributions

LG conceived the article. FN and LG wrote the first version of the manuscript with constructive input from EG. FN and EG generated display items under supervision from LG. All the authors approved the submitted version of the article.

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Correspondence to Lorenzo Galluzzi.

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Competing interests

LG holds research contracts with Lytix Biopharma, Promontory and Onxeo; has received consulting/advisory honoraria from Boehringer Ingelheim, AstraZeneca, AbbVie, OmniSEQ, Onxeo, The Longevity Labs, Inzen, Imvax, Sotio, Promontory, Noxopharm, EduCom, and the Luke Heller TECPR2 Foundation; and holds Promontory stock options. FN and EG have no conflicts of interest to declare.

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Naulin, F., Guilbaud, E. & Galluzzi, L. PARP7 and nucleic acid-driven oncosuppression. Cell Mol Immunol 21, 1177–1179 (2024). https://doi.org/10.1038/s41423-024-01182-6

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