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| Verfasst von: | Kirchner, Martina [VerfasserIn]  |
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| | Kluck, Klaus [VerfasserIn] |
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| | Brandt, Regine [VerfasserIn] |
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| | Volckmar, Anna-Lena [VerfasserIn] |
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| | Penzel, Roland [VerfasserIn] |
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| | Kazdal, Daniel [VerfasserIn] |
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| | Endris, Volker [VerfasserIn] |
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| | Neumann, Olaf [VerfasserIn] |
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| | Şeker-Cin, Huriye [VerfasserIn] |
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| | Goldschmid, Hannah [VerfasserIn] |
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| | Glade, Julia [VerfasserIn] |
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| | Allgäuer, Michael [VerfasserIn] |
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| | Kriegsmann, Mark [VerfasserIn] |
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| | Winter, Hauke [VerfasserIn] |
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| | Muley, Thomas [VerfasserIn] |
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| | Perner, Sven Roger [VerfasserIn] |
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| | Frost, N. [VerfasserIn] |
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| | Reck, M. [VerfasserIn] |
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| | Fröhling, Stefan [VerfasserIn] |
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| | Schirmacher, Peter [VerfasserIn] |
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| | Thomas, Michael [VerfasserIn] |
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| | Budczies, Jan [VerfasserIn] |
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| | Christopoulos, Petros [VerfasserIn] |
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| | Stenzinger, Albrecht [VerfasserIn] |
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| Titel: | The immune microenvironment in EGFR- and ERBB2-mutated lung adenocarcinoma |
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| Verf.angabe: | M. Kirchner, K. Kluck, R. Brandt, A.-L. Volckmar, R. Penzel, D. Kazdal, V. Endris, O. Neumann, H. Seker-Cin, H. Goldschmid, J. Glade, M. Allgäuer, M. Kriegsmann, H. Winter, T. Muley, S. Perner, N. Frost, M. Reck, S. Fröhling, P. Schirmacher, M. Thomas, J. Budczies, P. Christopoulos & A. Stenzinger |
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| E-Jahr: | 2021 |
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| Jahr: | 3 September 2021 |
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| Umfang: | 12 S. |
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| Fussnoten: | Gesehen am 28.01.2022 |
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| Titel Quelle: | Enthalten in: ESMO open |
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| Ort Quelle: | London : BMJ, 2016 |
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| Jahr Quelle: | 2021 |
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| Band/Heft Quelle: | 6(2021), 5, Artikel-ID 100253, Seite 1-12 |
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| ISSN Quelle: | 2059-7029 |
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| Abstract: | Background - Targeted therapies have improved survival and quality of life for patients with non-small-cell lung cancer with actionable driver mutations. However, epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 gene (HER2, also known as ERBB2) exon 20 insertions (Ex20mut) are characterized by a poor response to currently approved tyrosine kinase inhibitors and immunotherapies. The underlying immune biology is not well understood. - Materials and methods - We carried out messenger RNA expression profiling of lung adenocarcinomas (ADCs) with ERBB2 (n = 19) and EGFR exon 20-insertion mutations (n = 13) and compared these to tumors with classical EGFR mutations (n = 40, affecting EGFR exons 18, 19 or 21) and EGFR/ERBB2 mutation-negative lung ADC (EGFR/ERBB2wt, n = 26) focusing on immunologically relevant transcripts. Tumor-infiltrating immune cells were estimated from gene expression profiles. - Results - Cytotoxic cells were significantly lower in EGFR-mutated tumors regardless of the affected exon, while Th1 cells were significantly lower in EGFR-Ex20mut compared to EGFR/ERBB2wt tumors. We assessed the differentially expressed genes of ERBB2-Ex20mut and EGFR-Ex20mut tumors compared to EGFR-Ex18/19/21mut and EGFR/ERBB2wt tumors. Of these, the genes GUSB, HDAC11, IFNGR2, PUM1, RASGRF1 and RBL2 were up-regulated, while a lower expression of CBLC, GBP1, GBP2, GBP4 and MYC was observed in all three comparison groups. The omnibus test revealed 185 significantly (FDR = 5%) differentially expressed genes and we found these four most significant gene expression changes in the study cohort: VHL and JAK1 were overexpressed in ERBB2-Ex20mut and EGFR-Ex20mut tumors compared to both EGFR-Ex18/19/21mut and EGFR/ERBB2wt tumors. RIPK1 and STK11IP showed the highest expression in ERBB2-Ex20mut tumors. - Conclusions - Targeted gene expression profiling is a promising tool to read out the characteristics of the tumor microenvironment from routine diagnostic lung cancer biopsies. Significant immune reactivity and specific immunosuppressive characteristics in ERBB2-Ex20mut and EGFR-Ex20mut lung ADC with at least some degree of immune infiltration support further clinical evaluation of immune-modulators as partners of immune checkpoint inhibitors in such tumors. |
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| DOI: | doi:10.1016/j.esmoop.2021.100253 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: https://doi.org/10.1016/j.esmoop.2021.100253 |
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| | Volltext: https://www.sciencedirect.com/science/article/pii/S2059702921002143 |
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| | DOI: https://doi.org/10.1016/j.esmoop.2021.100253 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | EGFR exon 20 insertion |
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| | ERBB2 exon 20 insertion |
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| | immunosuppression |
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| | lung adenocarcinoma |
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| | tumor microenvironment |
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| K10plus-PPN: | 1787471489 |
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| Verknüpfungen: | → Zeitschrift |
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¬The¬ immune microenvironment in EGFR- and ERBB2-mutated lung adenocarcinoma / Kirchner, Martina [VerfasserIn]; 3 September 2021 (Online-Ressource)
