Immune landscape of the tumour microenvironment in Ethiopian breast cancer patients
Abstract Background The clinical management of breast cancer (BC) is mainly based on the assessment of receptor expression by tumour cells. However, there is still an unmet need for novel biomarkers important for prognosis and therapy. The tumour immune microenvironment (TIME) is thought to play a k...
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BMC
2024-11-01
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| Series: | Breast Cancer Research |
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| Online Access: | https://doi.org/10.1186/s13058-024-01916-4 |
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| author | Meron Yohannes Zelalem Desalegn Marcus Bauer Kathrin Stückrath Endale Anberbir Yonas Bekuretsion Mathewos Assefa Tariku Wakuma Yasin Worku Pablo S. C. Santos Lesley Taylor Adamu Adissie Claudia Wickenhauser Chiara Massa Martina Vetter Eva Johanna Kantelhardt Barbara Seliger Tamrat Abebe |
| author_facet | Meron Yohannes Zelalem Desalegn Marcus Bauer Kathrin Stückrath Endale Anberbir Yonas Bekuretsion Mathewos Assefa Tariku Wakuma Yasin Worku Pablo S. C. Santos Lesley Taylor Adamu Adissie Claudia Wickenhauser Chiara Massa Martina Vetter Eva Johanna Kantelhardt Barbara Seliger Tamrat Abebe |
| author_sort | Meron Yohannes |
| collection | DOAJ |
| description | Abstract Background The clinical management of breast cancer (BC) is mainly based on the assessment of receptor expression by tumour cells. However, there is still an unmet need for novel biomarkers important for prognosis and therapy. The tumour immune microenvironment (TIME) is thought to play a key role in prognosis and therapy selection, therefore this study aimed to describe the TIME in Ethiopian BC patients. Methods RNA was isolated from formalin-fixed paraffin-embedded (FFPE) tissue from 82 women with BC. Expression of PAM50 and 54 immune genes was analysed using the Nanostring platform and differentially expressed genes (DEGs) were determined using ROSALIND®. The abundance of different cell populations was estimated using Nanostring’s cell type profiling module, while tumour infiltrating lymphocytes (TILs) were analysed using haematoxylin and eosin (H&E) staining. In addition, the PIK3CA gene was genotyped for three hotspot mutations using qPCR. Kaplan-Meier survival analysis and log-rank test were performed to compare the prognostic relevance of immune subgroups. Results Four discrete immune phenotypes (IP1-4) were identified through hierarchical clustering of immune gene expression data. These IPs were characterized by DEGs associated with both immune activation and inhibition as well as variations in the extent of immune infiltration. However, there were no significant differences regarding PIK3CA mutations between the IPs. A downregulation of immune suppressive and activating genes and the lowest number of infiltrating immune cells were found in IP2, which was associated with luminal tumours. In contrast, IP4 displayed an active TME chracterized by an upregulation of cytotoxic genes and the highest density of immune cell infiltrations, independent of the specific intrinsic subtype. IP1 and IP3 exhibited intermediate characteristics. The IPs had a prognostic relevance and patients with an active TME had improved overall survival compared to IPs with a significant downregulation of the majority of immune genes. Conclusion Immune gene expression profiling identified four distinct immune contextures of the TME with unique gene expression patterns and immune infiltration. The classification into distinct immune subgroups may provide important information regarding prognosis and the selection of patients undergoing conventional treatments or immunotherapies. |
| format | Article |
| id | doaj-art-c816e041d2234f6cb299e121c841ba01 |
| institution | DOAJ |
| issn | 1465-542X |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Breast Cancer Research |
| spelling | doaj-art-c816e041d2234f6cb299e121c841ba012025-08-20T02:49:16ZengBMCBreast Cancer Research1465-542X2024-11-0126111310.1186/s13058-024-01916-4Immune landscape of the tumour microenvironment in Ethiopian breast cancer patientsMeron Yohannes0Zelalem Desalegn1Marcus Bauer2Kathrin Stückrath3Endale Anberbir4Yonas Bekuretsion5Mathewos Assefa6Tariku Wakuma7Yasin Worku8Pablo S. C. Santos9Lesley Taylor10Adamu Adissie11Claudia Wickenhauser12Chiara Massa13Martina Vetter14Eva Johanna Kantelhardt15Barbara Seliger16Tamrat Abebe17Department of Microbiology, Immunology & Parasitology, School of Medicine, Addis Ababa UniversityDepartment of Microbiology, Immunology & Parasitology, School of Medicine, Addis Ababa UniversityGlobal and Planetary Health Working Group, Institute of Medical Epidemiology, Biometrics and Informatics, Martin Luther University of Halle-WittenbergUniversity Clinic and Polyclinic for Gynecology, Martin Luther University of Halle-WittenbergDepartment of Surgery, School of Medicine, Addis Ababa UniversityDepartment of Pathology, School of Medicine, Addis Ababa UniversityDepartment of Oncology, School of Medicine, Addis Ababa UniversityAira HospitalSchool of Medicine, Wollo UniversityGlobal and Planetary Health Working Group, Institute of Medical Epidemiology, Biometrics and Informatics, Martin Luther University of Halle-WittenbergCity of Hope National Medical CenterGlobal and Planetary Health Working Group, Institute of Medical Epidemiology, Biometrics and Informatics, Martin Luther University of Halle-WittenbergInstitute of Pathology, Martin Luther University of Halle-WittenbergMedical Faculty, Martin Luther University of Halle-WittenbergUniversity Clinic and Polyclinic for Gynecology, Martin Luther University of Halle-WittenbergGlobal and Planetary Health Working Group, Institute of Medical Epidemiology, Biometrics and Informatics, Martin Luther University of Halle-WittenbergMedical Faculty, Martin Luther University of Halle-WittenbergDepartment of Microbiology, Immunology & Parasitology, School of Medicine, Addis Ababa UniversityAbstract Background The clinical management of breast cancer (BC) is mainly based on the assessment of receptor expression by tumour cells. However, there is still an unmet need for novel biomarkers important for prognosis and therapy. The tumour immune microenvironment (TIME) is thought to play a key role in prognosis and therapy selection, therefore this study aimed to describe the TIME in Ethiopian BC patients. Methods RNA was isolated from formalin-fixed paraffin-embedded (FFPE) tissue from 82 women with BC. Expression of PAM50 and 54 immune genes was analysed using the Nanostring platform and differentially expressed genes (DEGs) were determined using ROSALIND®. The abundance of different cell populations was estimated using Nanostring’s cell type profiling module, while tumour infiltrating lymphocytes (TILs) were analysed using haematoxylin and eosin (H&E) staining. In addition, the PIK3CA gene was genotyped for three hotspot mutations using qPCR. Kaplan-Meier survival analysis and log-rank test were performed to compare the prognostic relevance of immune subgroups. Results Four discrete immune phenotypes (IP1-4) were identified through hierarchical clustering of immune gene expression data. These IPs were characterized by DEGs associated with both immune activation and inhibition as well as variations in the extent of immune infiltration. However, there were no significant differences regarding PIK3CA mutations between the IPs. A downregulation of immune suppressive and activating genes and the lowest number of infiltrating immune cells were found in IP2, which was associated with luminal tumours. In contrast, IP4 displayed an active TME chracterized by an upregulation of cytotoxic genes and the highest density of immune cell infiltrations, independent of the specific intrinsic subtype. IP1 and IP3 exhibited intermediate characteristics. The IPs had a prognostic relevance and patients with an active TME had improved overall survival compared to IPs with a significant downregulation of the majority of immune genes. Conclusion Immune gene expression profiling identified four distinct immune contextures of the TME with unique gene expression patterns and immune infiltration. The classification into distinct immune subgroups may provide important information regarding prognosis and the selection of patients undergoing conventional treatments or immunotherapies.https://doi.org/10.1186/s13058-024-01916-4EthiopiaBreast cancerTumour immune microenvironmentImmune phenotypesPAM50 |
| spellingShingle | Meron Yohannes Zelalem Desalegn Marcus Bauer Kathrin Stückrath Endale Anberbir Yonas Bekuretsion Mathewos Assefa Tariku Wakuma Yasin Worku Pablo S. C. Santos Lesley Taylor Adamu Adissie Claudia Wickenhauser Chiara Massa Martina Vetter Eva Johanna Kantelhardt Barbara Seliger Tamrat Abebe Immune landscape of the tumour microenvironment in Ethiopian breast cancer patients Breast Cancer Research Ethiopia Breast cancer Tumour immune microenvironment Immune phenotypes PAM50 |
| title | Immune landscape of the tumour microenvironment in Ethiopian breast cancer patients |
| title_full | Immune landscape of the tumour microenvironment in Ethiopian breast cancer patients |
| title_fullStr | Immune landscape of the tumour microenvironment in Ethiopian breast cancer patients |
| title_full_unstemmed | Immune landscape of the tumour microenvironment in Ethiopian breast cancer patients |
| title_short | Immune landscape of the tumour microenvironment in Ethiopian breast cancer patients |
| title_sort | immune landscape of the tumour microenvironment in ethiopian breast cancer patients |
| topic | Ethiopia Breast cancer Tumour immune microenvironment Immune phenotypes PAM50 |
| url | https://doi.org/10.1186/s13058-024-01916-4 |
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