Deciphering the immunosuppressive tumor microenvironment in ALK- and EGFR-positive lung adenocarcinoma

  1. Budczies, Jan ORCID logo
  2. Kirchner, Martina
  3. Kluck, Klaus
  4. Kazdal, Daniel
  5. Glade, Julia
  6. Allgäuer, Michael
  7. Kriegsmann, Mark
  8. Heußel, Claus-Peter
  9. Herth, Felix J.
  10. Winter, Hauke
  11. Meister, Michael
  12. Muley, Thomas
  13. Goldmann, Torsten
  14. Fröhling, Stefan
  15. Wermke, Martin
  16. Waller, Cornelius F.
  17. Tufman, Amanda
  18. Reck, Martin
  19. Peters, Solange
  20. Schirmacher, Peter
  21. Thomas, Michael
  22. Christopoulos, Petros
  23. Stenzinger, Albrecht

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1000 Titel
  • Deciphering the immunosuppressive tumor microenvironment in ALK- and EGFR-positive lung adenocarcinoma
1000 Autor/in
  1. Budczies, Jan |
  2. Kirchner, Martina |
  3. Kluck, Klaus |
  4. Kazdal, Daniel |
  5. Glade, Julia |
  6. Allgäuer, Michael |
  7. Kriegsmann, Mark |
  8. Heußel, Claus-Peter |
  9. Herth, Felix J. |
  10. Winter, Hauke |
  11. Meister, Michael |
  12. Muley, Thomas |
  13. Goldmann, Torsten |
  14. Fröhling, Stefan |
  15. Wermke, Martin |
  16. Waller, Cornelius F. |
  17. Tufman, Amanda |
  18. Reck, Martin |
  19. Peters, Solange |
  20. Schirmacher, Peter |
  21. Thomas, Michael |
  22. Christopoulos, Petros |
  23. Stenzinger, Albrecht |
1000 Erscheinungsjahr 2021
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2021-06-14
1000 Erschienen in
1000 Quellenangabe
  • 71(2):251-265
1000 Copyrightjahr
  • 2021
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1007/s00262-021-02981-w |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8783861/ |
1000 Publikationsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Introduction!#!The advent of immune checkpoint blockade (ICB) has led to significantly improved disease outcome in lung adenocarcinoma (ADC), but response of ALK/EGFR-positive tumors to immune therapy is limited. The underlying immune biology is incompletely understood.!##!Methods!#!We performed comparative mRNA expression profiling of 31 ALK-positive, 40 EGFR-positive and 43 ALK/EGFR-negative lung ADC focused on immune gene expression. The presence and levels of tumor infiltration lymphocytes (TILs) as well as fourteen specific immune cell populations were estimated from the gene expression profiles.!##!Results!#!While total TILs were not lower in ALK-positive and EGFR-positive tumors compared to ALK/EGFR-negative tumors, specific immunosuppressive characteristics were detected in both subgroups: In ALK-positive tumors, regulatory T cells were significantly higher compared to EGFR-positive (fold change: FC = 1.9, p = 0.0013) and ALK/EGFR-negative tumors (FC = 2.1, p = 0.00047). In EGFR-positive tumors, cytotoxic cells were significantly lower compared to ALK-positive (FC =  - 1.7, p = 0.016) and to ALK/EGFR-negative tumors (FC =  - 2.1, p = 2.0E-05). A total number of 289 genes, 40 part of cytokine-cytokine receptor signaling, were differentially expressed between the three subgroups. Among the latter, five genes were differently expressed in both ALK-positive and EGFR-positive tumors, while twelve genes showed differential expression solely in ALK-positive tumors and eleven genes solely in EGFR-positive tumors.!##!Conclusion!#!Targeted gene expression profiling is a promising tool to read out tumor microenvironment characteristics from routine diagnostic lung cancer biopsies. Significant immune reactivity including specific immunosuppressive characteristics in ALK- and EGFR-positive lung ADC, but not a total absence of immune infiltration supports further clinical evaluation of immune-modulators as partners of ICB in such tumors.
1000 Sacherschließung
lokal Carcinoma, Non-Small-Cell Lung/metabolism [MeSH]
lokal Gene Expression Regulation, Neoplastic [MeSH]
lokal Aged, 80 and over [MeSH]
lokal Immune checkpoint blockade
lokal Aged [MeSH]
lokal ALK fusion
lokal ErbB Receptors/metabolism [MeSH]
lokal Original Article
lokal Tumor Cells, Cultured [MeSH]
lokal Male [MeSH]
lokal Lung Neoplasms/immunology [MeSH]
lokal Lung adenocarcinoma
lokal Carcinoma, Non-Small-Cell Lung/pathology [MeSH]
lokal EGFR mutation
lokal Female [MeSH]
lokal Follow-Up Studies [MeSH]
lokal Anaplastic Lymphoma Kinase/metabolism [MeSH]
lokal Adult [MeSH]
lokal Humans [MeSH]
lokal Retrospective Studies [MeSH]
lokal Middle Aged [MeSH]
lokal Adenocarcinoma of Lung/immunology [MeSH]
lokal Immunosuppression
lokal Adenocarcinoma of Lung/metabolism [MeSH]
lokal Lymphocytes, Tumor-Infiltrating/immunology [MeSH]
lokal Survival Rate [MeSH]
lokal Biomarkers, Tumor/metabolism [MeSH]
lokal Immunotherapy
lokal Prognosis [MeSH]
lokal Lung Neoplasms/pathology [MeSH]
lokal Carcinoma, Non-Small-Cell Lung/immunology [MeSH]
lokal Lung Neoplasms/metabolism [MeSH]
lokal Gene Expression Profiling [MeSH]
lokal Adenocarcinoma of Lung/pathology [MeSH]
lokal Tumor Microenvironment [MeSH]
1000 Liste der Beteiligten
  1. https://orcid.org/0000-0002-6668-5327|https://frl.publisso.de/adhoc/uri/S2lyY2huZXIsIE1hcnRpbmE=|https://frl.publisso.de/adhoc/uri/S2x1Y2ssIEtsYXVz|https://frl.publisso.de/adhoc/uri/S2F6ZGFsLCBEYW5pZWw=|https://frl.publisso.de/adhoc/uri/R2xhZGUsIEp1bGlh|https://frl.publisso.de/adhoc/uri/QWxsZ8OkdWVyLCBNaWNoYWVs|https://frl.publisso.de/adhoc/uri/S3JpZWdzbWFubiwgTWFyaw==|https://frl.publisso.de/adhoc/uri/SGV1w59lbCwgQ2xhdXMtUGV0ZXI=|https://frl.publisso.de/adhoc/uri/SGVydGgsIEZlbGl4IEou|https://frl.publisso.de/adhoc/uri/V2ludGVyLCBIYXVrZQ==|https://frl.publisso.de/adhoc/uri/TWVpc3RlciwgTWljaGFlbA==|https://frl.publisso.de/adhoc/uri/TXVsZXksIFRob21hcw==|https://frl.publisso.de/adhoc/uri/R29sZG1hbm4sIFRvcnN0ZW4=|https://frl.publisso.de/adhoc/uri/RnLDtmhsaW5nLCBTdGVmYW4=|https://frl.publisso.de/adhoc/uri/V2VybWtlLCBNYXJ0aW4=|https://frl.publisso.de/adhoc/uri/V2FsbGVyLCBDb3JuZWxpdXMgRi4=|https://frl.publisso.de/adhoc/uri/VHVmbWFuLCBBbWFuZGE=|https://frl.publisso.de/adhoc/uri/UmVjaywgTWFydGlu|https://frl.publisso.de/adhoc/uri/UGV0ZXJzLCBTb2xhbmdl|https://frl.publisso.de/adhoc/uri/U2NoaXJtYWNoZXIsIFBldGVy|https://frl.publisso.de/adhoc/uri/VGhvbWFzLCBNaWNoYWVs|https://frl.publisso.de/adhoc/uri/Q2hyaXN0b3BvdWxvcywgUGV0cm9z|https://frl.publisso.de/adhoc/uri/U3RlbnppbmdlciwgQWxicmVjaHQ=
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1000 Erstellt am 2023-05-11T13:27:07.565+0200
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1000 Zuletzt bearbeitet 2023-10-21T04:51:34.556+0200
1000 Objekt bearb. Sat Oct 21 04:51:34 CEST 2023
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