دورية أكاديمية
A2AR Expression and Immunosuppressive Environment Independent of KRAS and GNAS Mutations in Pseudomyxoma Peritonei.
| العنوان: | A2AR Expression and Immunosuppressive Environment Independent of KRAS and GNAS Mutations in Pseudomyxoma Peritonei. |
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| المؤلفون: | Kusamura S; Peritoneal Surface Malignancy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Busico A; Laboratory of Diagnostic and Molecular Research, Department of Diagnostic Innovation, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Conca E; Laboratory of Diagnostic and Molecular Research, Department of Diagnostic Innovation, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Capone I; Laboratory of Diagnostic and Molecular Research, Department of Diagnostic Innovation, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Agnelli L; Laboratory of Diagnostic and Molecular Research, Department of Diagnostic Innovation, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy.; Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Lorenzini D; Laboratory of Diagnostic and Molecular Research, Department of Diagnostic Innovation, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Brich S; Laboratory of Diagnostic and Molecular Research, Department of Diagnostic Innovation, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Angelini M; Laboratory of Diagnostic and Molecular Research, Department of Diagnostic Innovation, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Volpi CC; Laboratory of Diagnostic and Molecular Research, Department of Diagnostic Innovation, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Trupia DV; Laboratory of Diagnostic and Molecular Research, Department of Diagnostic Innovation, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Lagano V; 1st Pathology Division, Department of Diagnostic Innovation, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Torelli T; Laboratory of Diagnostic and Molecular Research, Department of Diagnostic Innovation, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Gloghini A; Laboratory of Diagnostic and Molecular Research, Department of Diagnostic Innovation, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Baratti D; Peritoneal Surface Malignancy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Guaglio M; Peritoneal Surface Malignancy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Milione M; 1st Pathology Division, Department of Diagnostic Innovation, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Deraco M; Peritoneal Surface Malignancy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy., Perrone F; Laboratory of Diagnostic and Molecular Research, Department of Diagnostic Innovation, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy. |
| المصدر: | Biomedicines [Biomedicines] 2023 Jul 20; Vol. 11 (7). Date of Electronic Publication: 2023 Jul 20. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: MDPI AG Country of Publication: Switzerland NLM ID: 101691304 Publication Model: Electronic Cited Medium: Print ISSN: 2227-9059 (Print) Linking ISSN: 22279059 NLM ISO Abbreviation: Biomedicines Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: Basel, Switzerland : MDPI AG, [2013]- |
| مستخلص: | In pseudomyxoma peritonei (PMP), KRAS and GNAS mutations are frequent. We hypothesized that these mutations may contribute to the suppression of antitumor immunity: KRAS may induce GMCSF expression, while GNAS may enhance the expression of cyclic adenosine monophosphate and A2AR signaling. This study aimed to explore possible mechanisms facilitated by KRAS and GNAS mutations for escaping immune surveillance. Additionally, we looked for new potential therapeutic and prognostic targets in this rare disease which is poorly characterized at the molecular level. GM-CSF, A2AR, CD73, CD39, and PD-L1 expression was investigated by immunohistochemistry in 40 PMPs characterized for GNAS and KRAS mutational status. Immune cell populations were studied by immunohistochemistry and nanostring nCounter ® . Following the criteria of a prognostic nomogram reported for PMP, we stratified the patients into two different risk groups, with 28 "low-risk" and 12 "high-risk" patients. We observed the expression of GM-CSF (74%); CD39 (37%); CD73 (53%); A2AR (74%); and PD-L1 (16%) which was unrelated to GNAS or KRAS status. The tumor microenvironment showed the presence of CD4+ T cells (86%); CD8+ T cells (27%); CD20+ B (67%); CD15+ cells (86%); and CD163+ M2 macrophages (67%), while CD56+ NK cells were absent. CD163 expression (27%) in PMP tumor cells was associated with poor prognosis. GNAS mutation and A2AR expression were not associated with a specific immune transcriptional signature. However, the expression assay revealed 21 genes associated with prognosis. The "high-risk" patients exhibited worse progression-free survival (HR = 2.3, CI 95%: 1.1-5.1, p = 0.034) and significant downregulation of MET , IL8 , PPARG , DTX4 , HMGA1, ZIC2 , WNT5B, and CCRL2 . In conclusion, we documented the presence of immunosuppressive factors such as GM-CSF, A2AR, and PD-L1 in PMP. These factors were not associated with GNAS and KRAS status and could be explored as therapeutic molecular targets. Additionally, a set of potential prognostic biomarkers, including CD163 expression in tumor cells, deserve further investigation. |
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| معلومات مُعتمدة: | AIRC IG 2016 Id.19206 Italian Association for Cancer Research |
| فهرسة مساهمة: | Keywords: A2AR; CD39; CD73; PDL-1; pseudomyxoma peritonei |
| تواريخ الأحداث: | Date Created: 20230729 Latest Revision: 20230731 |
| رمز التحديث: | 20230731 |
| مُعرف محوري في PubMed: | PMC10377259 |
| DOI: | 10.3390/biomedicines11072049 |
| PMID: | 37509688 |
| قاعدة البيانات: | MEDLINE |
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