دورية أكاديمية
Oncogenic Ras and ΔNp63α cooperate to recruit immunosuppressive polymorphonuclear myeloid-derived suppressor cells in a mouse model of squamous cancer pathogenesis.
| العنوان: | Oncogenic Ras and ΔNp63α cooperate to recruit immunosuppressive polymorphonuclear myeloid-derived suppressor cells in a mouse model of squamous cancer pathogenesis. |
|---|---|
| المؤلفون: | Sakakibara N; Office of Biotechnology Products, Center for Drug Evaluation and Research, FDA, Silver Spring, MD, United States., Clavijo PE; Translational Tumor Immunology, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD, United States., Sievers C; Translational Tumor Immunology, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD, United States., Gray VC; Office of Biotechnology Products, Center for Drug Evaluation and Research, FDA, Silver Spring, MD, United States., King KE; Office of Biotechnology Products, Center for Drug Evaluation and Research, FDA, Silver Spring, MD, United States., George AL; Office of Biotechnology Products, Center for Drug Evaluation and Research, FDA, Silver Spring, MD, United States., Ponnamperuma RM; Office of Biotechnology Products, Center for Drug Evaluation and Research, FDA, Silver Spring, MD, United States., Walter BA; Genitourinary Malignancies Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland, MD, United States., Chen Z; Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD, United States., Van Waes C; Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD, United States., Allen CT; Translational Tumor Immunology, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD, United States., Weinberg WC; Office of Biotechnology Products, Center for Drug Evaluation and Research, FDA, Silver Spring, MD, United States. |
| المصدر: | Frontiers in immunology [Front Immunol] 2023 Aug 10; Vol. 14, pp. 1200970. Date of Electronic Publication: 2023 Aug 10 (Print Publication: 2023). |
| نوع المنشور: | Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.; Research Support, N.I.H., Intramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Lausanne : Frontiers Research Foundation] |
| مواضيع طبية MeSH: | Myeloid-Derived Suppressor Cells* , Carcinoma, Squamous Cell*/genetics , Head and Neck Neoplasms*, Humans ; Animals ; Mice ; Immunosuppressive Agents ; Squamous Cell Carcinoma of Head and Neck ; Disease Models, Animal ; Tumor Microenvironment/genetics |
| مستخلص: | Introduction: Amplification of human chromosome 3q26-29, which encodes oncoprotein ΔNp63 among other isoforms of the p63 family, is a feature common to squamous cell carcinomas (SCCs) of multiple tissue origins. Along with overexpression of ΔNp63, activation of the protooncogene, RAS , whether by overexpression or oncogenic mutation, is frequently observed in many cancers. In this study, analysis of transcriptome data from The Cancer Genome Atlas (TCGA) demonstrated that expression of TP63 mRNA , particularly ΔNp63 isoforms, and HRAS are significantly elevated in advanced squamous cell carcinomas of the head and neck (HNSCCs), suggesting pathological significance. However, how co-overexpressed ΔNp63 and HRAS affect the immunosuppressive tumor microenvironment (TME) is incompletely understood. Methods: Here, we established and characterized an immune competent mouse model using primary keratinocytes with retroviral-mediated overexpression of ΔNp63α and constitutively activated HRAS (v-ras Ha G12R) to evaluate the role of these oncogenes in the immune TME. Results: In this model, orthotopic grafting of wildtype syngeneic keratinocytes expressing both v-ras Ha and elevated levels of ΔNp63α consistently yield carcinomas in syngeneic hosts, while cells expressing v-ras Ha alone yield predominantly papillomas. We found that polymorphonuclear (PMN) myeloid cells, experimentally validated to be immunosuppressive and thus representing myeloid-derived suppressor cells (PMN-MDSCs), were significantly recruited into the TME of carcinomas arising early following orthotopic grafting of ΔNp63α/v-ras Ha -expressing keratinocytes. ΔNp63α/v-ras Ha -driven carcinomas expressed higher levels of chemokines implicated in recruitment of MDSCs compared to v-ras Ha -initiated tumors, providing a heretofore undescribed link between ΔNp63α/HRAS-driven carcinomas and the development of an immunosuppressive TME. Conclusion: These results support the utilization of a genetic carcinogenesis model harboring specific genomic drivers of malignancy to study mechanisms underlying the development of local immunosuppression. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Sakakibara, Clavijo, Sievers, Gray, King, George, Ponnamperuma, Walter, Chen, Van Waes, Allen and Weinberg.) |
| References: | Oncogene. 2001 May 31;20(25):3193-205. (PMID: 11423969) Neoplasia. 2010 Dec;12(12):969-79. (PMID: 21170261) Cancer Immunol Res. 2019 Mar;7(3):401-413. (PMID: 30683733) Int J Mol Sci. 2019 Jul 23;20(14):. (PMID: 31340447) Clin Cancer Res. 2014 Dec 15;20(24):6582-92. (PMID: 25303977) J Clin Invest. 2013 Aug;123(8):3525-38. (PMID: 23867503) J Biol Chem. 1997 Sep 26;272(39):24113-6. (PMID: 9305854) J Invest Dermatol. 2011 Jun;131(6):1196-207. (PMID: 21471985) Cancer Res. 2014 Sep 1;74(17):4706-19. (PMID: 25035397) Cell. 2014 Aug 14;158(4):929-944. (PMID: 25109877) Sci Signal. 2016 Jun 21;9(433):ra62. (PMID: 27330189) Nat Commun. 2016 Aug 30;7:12601. (PMID: 27574101) Nature. 2015 Jan 29;517(7536):576-82. (PMID: 25631445) Cell Stem Cell. 2011 Feb 4;8(2):164-76. (PMID: 21295273) J Clin Invest. 2023 May 1;133(9):. (PMID: 36943390) J Clin Invest. 2018 Nov 1;128(11):5095-5109. (PMID: 30295647) Cell Rep. 2014 Oct 9;9(1):90-103. (PMID: 25263557) Nature. 1986 Oct 30-Nov 5;323(6091):822-4. (PMID: 2430189) Oral Oncol. 2016 Jul;58:59-70. (PMID: 27215705) Development. 2010 May;137(9):1431-9. (PMID: 20335364) Mol Cancer Ther. 2020 Sep;19(9):1784-1796. (PMID: 32727882) Cancer Res. 2009 Jan 1;69(1):319-28. (PMID: 19118017) J Invest Dermatol. 2017 Feb;137(2):494-505. (PMID: 27725202) Nat Commun. 2018 Sep 10;9(1):3667. (PMID: 30202019) Cancer Res. 2011 Nov 1;71(21):6867-77. (PMID: 21933882) Cell Rep. 2018 Apr 3;23(1):194-212.e6. (PMID: 29617660) Cancer Res. 2008 Jul 1;68(13):5122-31. (PMID: 18593911) J Exp Med. 1995 Jan 1;181(1):435-40. (PMID: 7807024) Cancer Res. 2015 Oct 1;75(19):4074-85. (PMID: 26294209) Oncogene. 2003 Jun 5;22(23):3635-44. (PMID: 12789272) Cytometry A. 2011 Feb;79(2):95-101. (PMID: 21265003) Front Immunol. 2018 Mar 02;9:398. (PMID: 29552012) Nucleic Acids Res. 2019 Jan 8;47(D1):D917-D922. (PMID: 30496479) Genes Dev. 2006 May 15;20(10):1331-42. (PMID: 16702406) Nucleic Acids Res. 2016 Jan 4;44(D1):D938-43. (PMID: 26673713) Cancer Res. 2017 May 15;77(10):2607-2619. (PMID: 28364000) Front Immunol. 2019 Feb 27;10:333. (PMID: 30873179) Cell Mol Life Sci. 2018 Apr;75(7):1179-1190. (PMID: 29103147) J Pathol. 2014 Feb;232(3):356-68. (PMID: 24258200) Oncogene. 2016 Nov 3;35(44):5781-5794. (PMID: 27132513) PLoS One. 2011;6(7):e21877. (PMID: 21789189) Cancer Discov. 2012 May;2(5):401-4. (PMID: 22588877) Cancer Res. 2011 May 15;71(10):3688-700. (PMID: 21576089) Cell Cycle. 2009 Nov 15;8(22):3702-6. (PMID: 19855172) Mol Carcinog. 2019 Sep;58(9):1571-1580. (PMID: 31286584) Nucleic Acids Res. 2012 Jan;40(Database issue):D947-56. (PMID: 22013161) J Exp Med. 2012 Aug 27;209(9):1689-702. (PMID: 22908325) Cell Mol Life Sci. 2018 Feb;75(4):689-713. (PMID: 29032503) Trends Immunol. 2016 Mar;37(3):208-220. (PMID: 26858199) Cell. 2017 Dec 14;171(7):1611-1624.e24. (PMID: 29198524) Nat Immunol. 2018 Feb;19(2):108-119. (PMID: 29348500) Cell. 2018 Apr 5;173(2):291-304.e6. (PMID: 29625048) Nat Protoc. 2008;3(5):799-810. (PMID: 18451788) Virchows Arch. 2013 Sep;463(3):415-25. (PMID: 23887585) Sci Signal. 2013 Apr 02;6(269):pl1. (PMID: 23550210) Nucleic Acids Res. 2009 Aug;37(15):5183-96. (PMID: 19561196) Nat Rev Immunol. 2017 Sep;17(9):559-572. (PMID: 28555670) Oncogene. 2000 Jul 20;19(31):3477-86. (PMID: 10918606) EMBO Mol Med. 2014 Jun 21;6(7):970-83. (PMID: 24952939) J Pathol. 2009 Oct;219(2):263-74. (PMID: 19718706) J Invest Dermatol. 2018 Jun;138(6):1360-1370. (PMID: 29288652) |
| معلومات مُعتمدة: | T32 DC000008 United States DC NIDCD NIH HHS; Z01 DC000016 United States ImNIH Intramural NIH HHS; Z01 DC000073 United States ImNIH Intramural NIH HHS; Z01 DC000074 United States ImNIH Intramural NIH HHS |
| فهرسة مساهمة: | Keywords: PMN-MDSC; carcinogenesis; in vivo; oncogenic; p63; ras; squamous; tumor micro environment (TME) |
| المشرفين على المادة: | 0 (Immunosuppressive Agents) |
| تواريخ الأحداث: | Date Created: 20230828 Date Completed: 20230829 Latest Revision: 20240722 |
| رمز التحديث: | 20240722 |
| مُعرف محوري في PubMed: | PMC10449460 |
| DOI: | 10.3389/fimmu.2023.1200970 |
| PMID: | 37638000 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1664-3224 |
|---|---|
| DOI: | 10.3389/fimmu.2023.1200970 |