Enhanced immune response outperform aggressive cancer biology and is associated with better survival in triple-negative breast cancer
Abstract Although the value of tumor-infiltrating lymphocytes is well known, the clinical relevance of an increased immune response, specifically in breast cancer, has not been investigated across large cohorts of patients using computational algorithms. Our hypothesis stated that an enhanced immune...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-08-01
|
| Series: | npj Breast Cancer |
| Online Access: | https://doi.org/10.1038/s41523-022-00466-2 |
| _version_ | 1797641992423866368 |
|---|---|
| author | Masanori Oshi Ankit Patel Rongrong Wu Lan Le Yoshihisa Tokumaru Akimitsu Yamada Li Yan Ryusei Matsuyama Takashi Ishikawa Itaru Endo Kazuaki Takabe |
| author_facet | Masanori Oshi Ankit Patel Rongrong Wu Lan Le Yoshihisa Tokumaru Akimitsu Yamada Li Yan Ryusei Matsuyama Takashi Ishikawa Itaru Endo Kazuaki Takabe |
| author_sort | Masanori Oshi |
| collection | DOAJ |
| description | Abstract Although the value of tumor-infiltrating lymphocytes is well known, the clinical relevance of an increased immune response, specifically in breast cancer, has not been investigated across large cohorts of patients using computational algorithms. Our hypothesis stated that an enhanced immune response is associated with an improvement in outcomes. To quantify the immune response, we utilized the allograft rejection score correlated with cytolytic activity and with all the other Hallmark immune-related gene sets. The score reflected the amount of infiltrating immune cells that correlated with the immune checkpoint molecule expressions, including CD4+ and CD8+ T cells, T helper type 1 (Th1) and type 2 (Th2) cells, M1 macrophages, B cells, and plasmacytoid dendritic cells (pDC). A high score was associated with high levels of intratumor heterogeneity, homologous recombination defects, mutation rate, histological grade, advanced stage, and lymph node metastasis. Breast malignancy with a high score enriched immune-related gene sets and pro-cancer-related gene sets, including epithelial–mesenchymal transition and KRAS pathway, in ER-positive/HER2-negative and triple-negative breast cancer (TNBC) groups. TNBC had the highest score compared to other subtypes, and was associated with better survival. In conclusion, we found that breast cancer with a high immune response is associated with aggressive cancer biology, but with better survival in TNBC. |
| first_indexed | 2024-03-11T13:53:44Z |
| format | Article |
| id | doaj.art-eaa72d2a8b7f490789450bdca11f1b29 |
| institution | Directory Open Access Journal |
| issn | 2374-4677 |
| language | English |
| last_indexed | 2024-03-11T13:53:44Z |
| publishDate | 2022-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Breast Cancer |
| spelling | doaj.art-eaa72d2a8b7f490789450bdca11f1b292023-11-02T07:43:08ZengNature Portfolionpj Breast Cancer2374-46772022-08-018111010.1038/s41523-022-00466-2Enhanced immune response outperform aggressive cancer biology and is associated with better survival in triple-negative breast cancerMasanori Oshi0Ankit Patel1Rongrong Wu2Lan Le3Yoshihisa Tokumaru4Akimitsu Yamada5Li Yan6Ryusei Matsuyama7Takashi Ishikawa8Itaru Endo9Kazuaki Takabe10Department of Surgical Oncology, Roswell Park Comprehensive Cancer CenterDepartment of Surgical Oncology, Roswell Park Comprehensive Cancer CenterDepartment of Surgical Oncology, Roswell Park Comprehensive Cancer CenterDepartment of Surgical Oncology, Roswell Park Comprehensive Cancer CenterDepartment of Surgical Oncology, Roswell Park Comprehensive Cancer CenterDepartment of Gastroenterological Surgery, Yokohama City University Graduate School of MedicineDepartment of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer CenterDepartment of Gastroenterological Surgery, Yokohama City University Graduate School of MedicineDepartment of Breast Surgery and Oncology, Tokyo Medical UniversityDepartment of Gastroenterological Surgery, Yokohama City University Graduate School of MedicineDepartment of Surgical Oncology, Roswell Park Comprehensive Cancer CenterAbstract Although the value of tumor-infiltrating lymphocytes is well known, the clinical relevance of an increased immune response, specifically in breast cancer, has not been investigated across large cohorts of patients using computational algorithms. Our hypothesis stated that an enhanced immune response is associated with an improvement in outcomes. To quantify the immune response, we utilized the allograft rejection score correlated with cytolytic activity and with all the other Hallmark immune-related gene sets. The score reflected the amount of infiltrating immune cells that correlated with the immune checkpoint molecule expressions, including CD4+ and CD8+ T cells, T helper type 1 (Th1) and type 2 (Th2) cells, M1 macrophages, B cells, and plasmacytoid dendritic cells (pDC). A high score was associated with high levels of intratumor heterogeneity, homologous recombination defects, mutation rate, histological grade, advanced stage, and lymph node metastasis. Breast malignancy with a high score enriched immune-related gene sets and pro-cancer-related gene sets, including epithelial–mesenchymal transition and KRAS pathway, in ER-positive/HER2-negative and triple-negative breast cancer (TNBC) groups. TNBC had the highest score compared to other subtypes, and was associated with better survival. In conclusion, we found that breast cancer with a high immune response is associated with aggressive cancer biology, but with better survival in TNBC.https://doi.org/10.1038/s41523-022-00466-2 |
| spellingShingle | Masanori Oshi Ankit Patel Rongrong Wu Lan Le Yoshihisa Tokumaru Akimitsu Yamada Li Yan Ryusei Matsuyama Takashi Ishikawa Itaru Endo Kazuaki Takabe Enhanced immune response outperform aggressive cancer biology and is associated with better survival in triple-negative breast cancer npj Breast Cancer |
| title | Enhanced immune response outperform aggressive cancer biology and is associated with better survival in triple-negative breast cancer |
| title_full | Enhanced immune response outperform aggressive cancer biology and is associated with better survival in triple-negative breast cancer |
| title_fullStr | Enhanced immune response outperform aggressive cancer biology and is associated with better survival in triple-negative breast cancer |
| title_full_unstemmed | Enhanced immune response outperform aggressive cancer biology and is associated with better survival in triple-negative breast cancer |
| title_short | Enhanced immune response outperform aggressive cancer biology and is associated with better survival in triple-negative breast cancer |
| title_sort | enhanced immune response outperform aggressive cancer biology and is associated with better survival in triple negative breast cancer |
| url | https://doi.org/10.1038/s41523-022-00466-2 |
| work_keys_str_mv | AT masanorioshi enhancedimmuneresponseoutperformaggressivecancerbiologyandisassociatedwithbettersurvivalintriplenegativebreastcancer AT ankitpatel enhancedimmuneresponseoutperformaggressivecancerbiologyandisassociatedwithbettersurvivalintriplenegativebreastcancer AT rongrongwu enhancedimmuneresponseoutperformaggressivecancerbiologyandisassociatedwithbettersurvivalintriplenegativebreastcancer AT lanle enhancedimmuneresponseoutperformaggressivecancerbiologyandisassociatedwithbettersurvivalintriplenegativebreastcancer AT yoshihisatokumaru enhancedimmuneresponseoutperformaggressivecancerbiologyandisassociatedwithbettersurvivalintriplenegativebreastcancer AT akimitsuyamada enhancedimmuneresponseoutperformaggressivecancerbiologyandisassociatedwithbettersurvivalintriplenegativebreastcancer AT liyan enhancedimmuneresponseoutperformaggressivecancerbiologyandisassociatedwithbettersurvivalintriplenegativebreastcancer AT ryuseimatsuyama enhancedimmuneresponseoutperformaggressivecancerbiologyandisassociatedwithbettersurvivalintriplenegativebreastcancer AT takashiishikawa enhancedimmuneresponseoutperformaggressivecancerbiologyandisassociatedwithbettersurvivalintriplenegativebreastcancer AT itaruendo enhancedimmuneresponseoutperformaggressivecancerbiologyandisassociatedwithbettersurvivalintriplenegativebreastcancer AT kazuakitakabe enhancedimmuneresponseoutperformaggressivecancerbiologyandisassociatedwithbettersurvivalintriplenegativebreastcancer |