Investigating the Prognostic Relevance of Tumor Immune Microenvironment and Immune Gene Assembly in Breast Carcinoma Subtypes
We hypothesized that different BC subtypes are characterized by spatially distinct tumor immune microenvironment (TIME) and that immune gene assembly of metastatic (Met) and non-metastatic (Ctrl) BCs vary across subtypes. Peritumoral, stromal and intratumoral TIL was assessed on 309 BC cases. Hot, c...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-04-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/8/1942 |
| _version_ | 1797436502873997312 |
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| author | Beáta Szeitz Orsolya Pipek Janina Kulka Csilla Szundi Orsolya Rusz Tímea Tőkés Attila Marcell Szász Kristóf Attila Kovács Adrián Pesti Taya Beri Ben Arie Ambrus Gángó Zsolt Fülöp Emőke Drágus Stefan A. Vári-Kakas Anna Mária Tőkés |
| author_facet | Beáta Szeitz Orsolya Pipek Janina Kulka Csilla Szundi Orsolya Rusz Tímea Tőkés Attila Marcell Szász Kristóf Attila Kovács Adrián Pesti Taya Beri Ben Arie Ambrus Gángó Zsolt Fülöp Emőke Drágus Stefan A. Vári-Kakas Anna Mária Tőkés |
| author_sort | Beáta Szeitz |
| collection | DOAJ |
| description | We hypothesized that different BC subtypes are characterized by spatially distinct tumor immune microenvironment (TIME) and that immune gene assembly of metastatic (Met) and non-metastatic (Ctrl) BCs vary across subtypes. Peritumoral, stromal and intratumoral TIL was assessed on 309 BC cases. Hot, cold and immune-excluded groups were defined, and the prognostic role of this classification was assessed. CD4<sup>+</sup>/CD8<sup>+</sup> positivity was analyzed in 75 cases in four systematically predefined tumor regions. Immune gene expression of Met and Ctrl HER2-negative BCs was compared by using NanoString nCounter technology. The amount of TIL infiltration varied greatly within all BC subtypes. Two-third of the cases were cold tumors with no significant survival difference compared to hot tumors. A lower CD4<sup>+</sup>/CD8<sup>+</sup> ratio at the stromal internal tumor region was significantly associated with longer distant metastasis-free survival. The differentially expressed immune genes between Met and Ctrl varied across the studied BC subtypes with TNBC showing distinct features from the luminal subtypes. The TIME is characterized by a considerable heterogeneity; however, low level of TILs does not equate to disease progression. The differences in immune gene expression observed between Met and Ctrl breast carcinomas call attention to the important role of altered immune function in BC progression. |
| first_indexed | 2024-03-09T11:03:35Z |
| format | Article |
| id | doaj.art-c9ce54cfa5524ba6bd765f6aefc0a2f1 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T11:03:35Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-c9ce54cfa5524ba6bd765f6aefc0a2f12023-12-01T01:06:25ZengMDPI AGCancers2072-66942022-04-01148194210.3390/cancers14081942Investigating the Prognostic Relevance of Tumor Immune Microenvironment and Immune Gene Assembly in Breast Carcinoma SubtypesBeáta Szeitz0Orsolya Pipek1Janina Kulka2Csilla Szundi3Orsolya Rusz4Tímea Tőkés5Attila Marcell Szász6Kristóf Attila Kovács7Adrián Pesti8Taya Beri Ben Arie9Ambrus Gángó10Zsolt Fülöp11Emőke Drágus12Stefan A. Vári-Kakas13Anna Mária Tőkés14Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, HungaryDepartment of Physics of Complex Systems, Institute of Physics, Eötvös Loránd University, 1117 Budapest, HungaryDepartment of Pathology, Forensic and Insurance Medicine, Semmelweis University, 1091 Budapest, HungaryDepartment of Pathology, Forensic and Insurance Medicine, Semmelweis University, 1091 Budapest, HungaryDepartment of Pathology, Forensic and Insurance Medicine, SE NAP, Brain Metastasis Research Group, Semmelweis University, 1091 Budapest, HungaryDivision of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, HungaryDivision of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, HungaryDepartment of Pathology, Forensic and Insurance Medicine, Semmelweis University, 1091 Budapest, HungaryDepartment of Pathology, Forensic and Insurance Medicine, Semmelweis University, 1091 Budapest, HungaryDepartment of Pathology, Forensic and Insurance Medicine, Semmelweis University, 1091 Budapest, HungaryMTA-SE Momentum Molecular Oncohematology Research Group, 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, 1085 Budapest, HungaryDepartment of Surgery, George Emil Palade University of Medicine, Pharmacy, Science and Technology, 540139 Targu Mures, RomaniaDepartment of Urology, Clinical County Hospital, 540167 Targu Mures, RomaniaFaculty of Electrical Engineering and Information Technology, University of Oradea, Str. Universitatii nr. 1, 410087 Oradea, RomaniaDepartment of Pathology, Forensic and Insurance Medicine, Semmelweis University, 1091 Budapest, HungaryWe hypothesized that different BC subtypes are characterized by spatially distinct tumor immune microenvironment (TIME) and that immune gene assembly of metastatic (Met) and non-metastatic (Ctrl) BCs vary across subtypes. Peritumoral, stromal and intratumoral TIL was assessed on 309 BC cases. Hot, cold and immune-excluded groups were defined, and the prognostic role of this classification was assessed. CD4<sup>+</sup>/CD8<sup>+</sup> positivity was analyzed in 75 cases in four systematically predefined tumor regions. Immune gene expression of Met and Ctrl HER2-negative BCs was compared by using NanoString nCounter technology. The amount of TIL infiltration varied greatly within all BC subtypes. Two-third of the cases were cold tumors with no significant survival difference compared to hot tumors. A lower CD4<sup>+</sup>/CD8<sup>+</sup> ratio at the stromal internal tumor region was significantly associated with longer distant metastasis-free survival. The differentially expressed immune genes between Met and Ctrl varied across the studied BC subtypes with TNBC showing distinct features from the luminal subtypes. The TIME is characterized by a considerable heterogeneity; however, low level of TILs does not equate to disease progression. The differences in immune gene expression observed between Met and Ctrl breast carcinomas call attention to the important role of altered immune function in BC progression.https://www.mdpi.com/2072-6694/14/8/1942breast carcinoma subtypesTILimmune-related geneNanoStringCD4<sup>+</sup> T cellsCD8<sup>+</sup> T cells |
| spellingShingle | Beáta Szeitz Orsolya Pipek Janina Kulka Csilla Szundi Orsolya Rusz Tímea Tőkés Attila Marcell Szász Kristóf Attila Kovács Adrián Pesti Taya Beri Ben Arie Ambrus Gángó Zsolt Fülöp Emőke Drágus Stefan A. Vári-Kakas Anna Mária Tőkés Investigating the Prognostic Relevance of Tumor Immune Microenvironment and Immune Gene Assembly in Breast Carcinoma Subtypes Cancers breast carcinoma subtypes TIL immune-related gene NanoString CD4<sup>+</sup> T cells CD8<sup>+</sup> T cells |
| title | Investigating the Prognostic Relevance of Tumor Immune Microenvironment and Immune Gene Assembly in Breast Carcinoma Subtypes |
| title_full | Investigating the Prognostic Relevance of Tumor Immune Microenvironment and Immune Gene Assembly in Breast Carcinoma Subtypes |
| title_fullStr | Investigating the Prognostic Relevance of Tumor Immune Microenvironment and Immune Gene Assembly in Breast Carcinoma Subtypes |
| title_full_unstemmed | Investigating the Prognostic Relevance of Tumor Immune Microenvironment and Immune Gene Assembly in Breast Carcinoma Subtypes |
| title_short | Investigating the Prognostic Relevance of Tumor Immune Microenvironment and Immune Gene Assembly in Breast Carcinoma Subtypes |
| title_sort | investigating the prognostic relevance of tumor immune microenvironment and immune gene assembly in breast carcinoma subtypes |
| topic | breast carcinoma subtypes TIL immune-related gene NanoString CD4<sup>+</sup> T cells CD8<sup>+</sup> T cells |
| url | https://www.mdpi.com/2072-6694/14/8/1942 |
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