Whole stromal fibroblast signature is linked to specific chemokine and immune infiltration patterns and to improved survival in NSCLC
ABSTRACTCancer associated fibroblasts (CAF) are known to orchestrate multiple components of the tumor microenvironment, whereas the influence of the whole stromal-fibroblast compartment is less understood. Here, an extended stromal fibroblast signature was investigated to define its impact on immune...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2023.2274130 |
| _version_ | 1797367146408312832 |
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| author | Stefan Koeck Arno Amann Johan Kern Marit Zwierzina Edith Lorenz Sieghart Sopper Heinz Zwierzina Finn Mildner Martina Sykora Susanne Sprung Hubert Hackl Florian Augustin Hubert T. Maier Andreas Pircher Georg Pall Dominik Wolf Gabriele Gamerith |
| author_facet | Stefan Koeck Arno Amann Johan Kern Marit Zwierzina Edith Lorenz Sieghart Sopper Heinz Zwierzina Finn Mildner Martina Sykora Susanne Sprung Hubert Hackl Florian Augustin Hubert T. Maier Andreas Pircher Georg Pall Dominik Wolf Gabriele Gamerith |
| author_sort | Stefan Koeck |
| collection | DOAJ |
| description | ABSTRACTCancer associated fibroblasts (CAF) are known to orchestrate multiple components of the tumor microenvironment, whereas the influence of the whole stromal-fibroblast compartment is less understood. Here, an extended stromal fibroblast signature was investigated to define its impact on immune cell infiltration. The lung cancer adenocarcinoma (LUAD) data set of the cancer genome atlas (TCGA) was used to test whole stroma signatures and cancer-associated fibroblast signatures for their impact on prognosis. 3D cell cultures of the NSCLC cancer cell line A549 together with the fibroblast cell line SV80 were used in combination with infiltrating peripheral blood mononuclear cells (PBMC) for in-vitro investigations. Immune cell infiltration was assessed via flow cytometry, chemokines were analyzed by immunoassays and RNA microarrays. Results were confirmed in specimens from NSCLC patients by flow cytometry or immunohistochemistry as well as in the TCGA data set. The TCGA analyses correlated the whole stromal-fibroblast signature with an improved outcome, whereas no effect was found for the CAF signatures. In 3D microtumors, the presence of fibroblasts induced infiltration of B cells and CD69+CD4+ T cells, which was linked to an increased expression of CCL13 and CXCL16. The stroma/lymphocyte interaction was confirmed in NSCLC patients, as stroma-rich tumors displayed an elevated B cell count and survival in the local cohort and the TCGA data set. A whole stromal fibroblast signature was associated with an improved clinical outcome in lung adenocarcinoma and in vitro and in vivo experiments suggest that this signature increases B and T cell recruitment via induction of chemokines. |
| first_indexed | 2024-03-08T17:13:14Z |
| format | Article |
| id | doaj.art-b8859450d2444344a0b717d8fca9bf03 |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-03-08T17:13:14Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-b8859450d2444344a0b717d8fca9bf032024-01-03T19:25:36ZengTaylor & Francis GroupOncoImmunology2162-402X2023-12-0112110.1080/2162402X.2023.2274130Whole stromal fibroblast signature is linked to specific chemokine and immune infiltration patterns and to improved survival in NSCLCStefan Koeck0Arno Amann1Johan Kern2Marit Zwierzina3Edith Lorenz4Sieghart Sopper5Heinz Zwierzina6Finn Mildner7Martina Sykora8Susanne Sprung9Hubert Hackl10Florian Augustin11Hubert T. Maier12Andreas Pircher13Georg Pall14Dominik Wolf15Gabriele Gamerith16Department of Internal Medicine V, Medical University of Innsbruck, Innsbruck, Tyrol, AustriaDepartment of Internal Medicine V, Medical University of Innsbruck, Innsbruck, Tyrol, AustriaDepartment of Internal Medicine V, Medical University of Innsbruck, Innsbruck, Tyrol, AustriaDepartment of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Innsbruck, Innsbruck, AustriaDepartment of Internal Medicine V, Medical University of Innsbruck, Innsbruck, Tyrol, AustriaDepartment of Internal Medicine V, Medical University of Innsbruck, Innsbruck, Tyrol, AustriaDepartment of Internal Medicine V, Medical University of Innsbruck, Innsbruck, Tyrol, AustriaDepartment of Internal Medicine V, Medical University of Innsbruck, Innsbruck, Tyrol, AustriaDepartment of Internal Medicine V, Medical University of Innsbruck, Innsbruck, Tyrol, AustriaDepartment of Pathology, Neuropathology, and Molecular Pathology, Medical University of Innsbruck, Innsbruck, Tyrol, AustriaInstitute of Bioinformatics, Biocenter, Medical University of Innsbruck, Innsbruck, Tyrol, AustriaDepartment of Visceral, Transplant and Thoracic Surgery, Center of Operative Medicine, Medical University of Innsbruck, Innsbruck, Tyrol, AustriaDepartment of Visceral, Transplant and Thoracic Surgery, Center of Operative Medicine, Medical University of Innsbruck, Innsbruck, Tyrol, AustriaDepartment of Internal Medicine V, Medical University of Innsbruck, Innsbruck, Tyrol, AustriaDepartment of Internal Medicine V, Medical University of Innsbruck, Innsbruck, Tyrol, AustriaDepartment of Internal Medicine V, Medical University of Innsbruck, Innsbruck, Tyrol, AustriaDepartment of Internal Medicine V, Medical University of Innsbruck, Innsbruck, Tyrol, AustriaABSTRACTCancer associated fibroblasts (CAF) are known to orchestrate multiple components of the tumor microenvironment, whereas the influence of the whole stromal-fibroblast compartment is less understood. Here, an extended stromal fibroblast signature was investigated to define its impact on immune cell infiltration. The lung cancer adenocarcinoma (LUAD) data set of the cancer genome atlas (TCGA) was used to test whole stroma signatures and cancer-associated fibroblast signatures for their impact on prognosis. 3D cell cultures of the NSCLC cancer cell line A549 together with the fibroblast cell line SV80 were used in combination with infiltrating peripheral blood mononuclear cells (PBMC) for in-vitro investigations. Immune cell infiltration was assessed via flow cytometry, chemokines were analyzed by immunoassays and RNA microarrays. Results were confirmed in specimens from NSCLC patients by flow cytometry or immunohistochemistry as well as in the TCGA data set. The TCGA analyses correlated the whole stromal-fibroblast signature with an improved outcome, whereas no effect was found for the CAF signatures. In 3D microtumors, the presence of fibroblasts induced infiltration of B cells and CD69+CD4+ T cells, which was linked to an increased expression of CCL13 and CXCL16. The stroma/lymphocyte interaction was confirmed in NSCLC patients, as stroma-rich tumors displayed an elevated B cell count and survival in the local cohort and the TCGA data set. A whole stromal fibroblast signature was associated with an improved clinical outcome in lung adenocarcinoma and in vitro and in vivo experiments suggest that this signature increases B and T cell recruitment via induction of chemokines.https://www.tandfonline.com/doi/10.1080/2162402X.2023.2274130CAFcancerco-cultureimmune cellsinfiltrationmicroenvironment |
| spellingShingle | Stefan Koeck Arno Amann Johan Kern Marit Zwierzina Edith Lorenz Sieghart Sopper Heinz Zwierzina Finn Mildner Martina Sykora Susanne Sprung Hubert Hackl Florian Augustin Hubert T. Maier Andreas Pircher Georg Pall Dominik Wolf Gabriele Gamerith Whole stromal fibroblast signature is linked to specific chemokine and immune infiltration patterns and to improved survival in NSCLC OncoImmunology CAF cancer co-culture immune cells infiltration microenvironment |
| title | Whole stromal fibroblast signature is linked to specific chemokine and immune infiltration patterns and to improved survival in NSCLC |
| title_full | Whole stromal fibroblast signature is linked to specific chemokine and immune infiltration patterns and to improved survival in NSCLC |
| title_fullStr | Whole stromal fibroblast signature is linked to specific chemokine and immune infiltration patterns and to improved survival in NSCLC |
| title_full_unstemmed | Whole stromal fibroblast signature is linked to specific chemokine and immune infiltration patterns and to improved survival in NSCLC |
| title_short | Whole stromal fibroblast signature is linked to specific chemokine and immune infiltration patterns and to improved survival in NSCLC |
| title_sort | whole stromal fibroblast signature is linked to specific chemokine and immune infiltration patterns and to improved survival in nsclc |
| topic | CAF cancer co-culture immune cells infiltration microenvironment |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2023.2274130 |
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