The Impact of Immunofunctional Phenotyping on the Malfunction of the Cancer Immunity Cycle in Breast Cancer
The cancer-immunity cycle (CIC) is a series of self-sustaining stepwise events to fight cancer growth by the immune system. We hypothesized that immunofunctional phenotyping that represent the malfunction of the CIC is clinically relevant in breast cancer (BC). Total of 2979 BC cases; 1075 from TCGA...
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| Format: | Article |
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MDPI AG
2020-12-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/1/110 |
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| author | Takashi Takeshita Toshihiko Torigoe Li Yan Jing Li Huang Hiroko Yamashita Kazuaki Takabe |
| author_facet | Takashi Takeshita Toshihiko Torigoe Li Yan Jing Li Huang Hiroko Yamashita Kazuaki Takabe |
| author_sort | Takashi Takeshita |
| collection | DOAJ |
| description | The cancer-immunity cycle (CIC) is a series of self-sustaining stepwise events to fight cancer growth by the immune system. We hypothesized that immunofunctional phenotyping that represent the malfunction of the CIC is clinically relevant in breast cancer (BC). Total of 2979 BC cases; 1075 from TCGA cohort, 1904 from METABRIC cohort were analyzed. The immunofunctional phenotype was classified as follows: hot T-cell infiltrated (HTI), high immune cytolytic activity (CYT), Cold T-cell infiltrated (CTI), high frequency of CD8+ T cells and low CYT, and non-inflamed, low frequency of CD8+ T cells and low CYT. The analysis of tumor immune microenvironment in the immunofunctional phenotype revealed that not only immunostimulatory factors, but also immunosuppressive factors were significantly elevated and immunosuppressive cells were significantly decreased in HTI. Patients in HTI were significantly associated with better survival in whole cohort and patients in CTI were significantly associated with worse survival in triple negative. Furthers, HTI was inversely related to estrogen responsive signaling. We demonstrated that immunofunctional phenotype not only indicated the degree of anti-cancer immune dysfunction, but also served as a prognostic biomarker and HTI was inversely related to estrogen response. |
| first_indexed | 2024-03-10T13:35:41Z |
| format | Article |
| id | doaj.art-45de41765b8c4da6a562f6d0b645ed26 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T13:35:41Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-45de41765b8c4da6a562f6d0b645ed262023-11-21T07:31:56ZengMDPI AGCancers2072-66942020-12-0113111010.3390/cancers13010110The Impact of Immunofunctional Phenotyping on the Malfunction of the Cancer Immunity Cycle in Breast CancerTakashi Takeshita0Toshihiko Torigoe1Li Yan2Jing Li Huang3Hiroko Yamashita4Kazuaki Takabe5Department of Breast Surgery, Hokkaido University Hospital, Hokkaido 060-8648, JapanDepartment of Pathology, Sapporo Medical University School of Medicine, Hokkaido 060-8556, JapanDepartment of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 10001, USADepartment of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263, USADepartment of Breast Surgery, Hokkaido University Hospital, Hokkaido 060-8648, JapanDepartment of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263, USAThe cancer-immunity cycle (CIC) is a series of self-sustaining stepwise events to fight cancer growth by the immune system. We hypothesized that immunofunctional phenotyping that represent the malfunction of the CIC is clinically relevant in breast cancer (BC). Total of 2979 BC cases; 1075 from TCGA cohort, 1904 from METABRIC cohort were analyzed. The immunofunctional phenotype was classified as follows: hot T-cell infiltrated (HTI), high immune cytolytic activity (CYT), Cold T-cell infiltrated (CTI), high frequency of CD8+ T cells and low CYT, and non-inflamed, low frequency of CD8+ T cells and low CYT. The analysis of tumor immune microenvironment in the immunofunctional phenotype revealed that not only immunostimulatory factors, but also immunosuppressive factors were significantly elevated and immunosuppressive cells were significantly decreased in HTI. Patients in HTI were significantly associated with better survival in whole cohort and patients in CTI were significantly associated with worse survival in triple negative. Furthers, HTI was inversely related to estrogen responsive signaling. We demonstrated that immunofunctional phenotype not only indicated the degree of anti-cancer immune dysfunction, but also served as a prognostic biomarker and HTI was inversely related to estrogen response.https://www.mdpi.com/2072-6694/13/1/110breast cancerthe cancer immunity cyclecancer genomicstumor immune microenvironmentbioinformatics |
| spellingShingle | Takashi Takeshita Toshihiko Torigoe Li Yan Jing Li Huang Hiroko Yamashita Kazuaki Takabe The Impact of Immunofunctional Phenotyping on the Malfunction of the Cancer Immunity Cycle in Breast Cancer Cancers breast cancer the cancer immunity cycle cancer genomics tumor immune microenvironment bioinformatics |
| title | The Impact of Immunofunctional Phenotyping on the Malfunction of the Cancer Immunity Cycle in Breast Cancer |
| title_full | The Impact of Immunofunctional Phenotyping on the Malfunction of the Cancer Immunity Cycle in Breast Cancer |
| title_fullStr | The Impact of Immunofunctional Phenotyping on the Malfunction of the Cancer Immunity Cycle in Breast Cancer |
| title_full_unstemmed | The Impact of Immunofunctional Phenotyping on the Malfunction of the Cancer Immunity Cycle in Breast Cancer |
| title_short | The Impact of Immunofunctional Phenotyping on the Malfunction of the Cancer Immunity Cycle in Breast Cancer |
| title_sort | impact of immunofunctional phenotyping on the malfunction of the cancer immunity cycle in breast cancer |
| topic | breast cancer the cancer immunity cycle cancer genomics tumor immune microenvironment bioinformatics |
| url | https://www.mdpi.com/2072-6694/13/1/110 |
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