The prognostic value of a combined immune score in tumor and immune cells assessed by immunohistochemistry in triple-negative breast cancer
Abstract Background This study aimed to develop a novel combined immune score (CIS)-based model assessing prognosis in triple-negative breast cancer (TNBC). Methods The expression of eight immune markers (PD-1, PD-L1, PD-L2, IDO, TIM3, OX40, OX40L, and H7-H2) was assessed with immunohistochemistry o...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-11-01
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| Series: | Breast Cancer Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13058-023-01710-8 |
| _version_ | 1797636657495670784 |
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| author | Ji Eun Choi Jae Seok Lee Min-Sun Jin Ilias P. Nikas Kwangsoo Kim Sunah Yang Soo Young Park Jiwon Koh Sohyeon Yang Seock-Ah Im Han Suk Ryu |
| author_facet | Ji Eun Choi Jae Seok Lee Min-Sun Jin Ilias P. Nikas Kwangsoo Kim Sunah Yang Soo Young Park Jiwon Koh Sohyeon Yang Seock-Ah Im Han Suk Ryu |
| author_sort | Ji Eun Choi |
| collection | DOAJ |
| description | Abstract Background This study aimed to develop a novel combined immune score (CIS)-based model assessing prognosis in triple-negative breast cancer (TNBC). Methods The expression of eight immune markers (PD-1, PD-L1, PD-L2, IDO, TIM3, OX40, OX40L, and H7-H2) was assessed with immunohistochemistry on the tumor cells (TCs) and immune cells (ICs) of 227 TNBC cases, respectively, and subsequently associated with selected clinicopathological parameters and survival. Data retrieved from The Cancer Genome Atlas (TCGA) were further examined to validate our findings. Results All immune markers were often expressed in TCs and ICs, except for PD-1 which was not expressed in TCs. In ICs, the expression of all immune markers was positively correlated between one another, except between PD-L1 and OX40, also TIM3 and OX40. In ICs, PD-1, PD-L1, and OX40L positive expression was associated with a longer progression-free survival (PFS; p = 0.040, p = 0.020, and p = 0.020, respectively). In TCs, OX40 positive expression was associated with a shorter PFS (p = 0.025). Subsequently, the TNBC patients were classified into high and low combined immune score groups (CIS-H and CIS-L), based on the expression levels of a selection of biomarkers in TCs (TCIS-H or TCIS-L) and ICs (ICIS-H or ICIS-L). The TCIS-H group was significantly associated with a longer PFS (p < 0.001). Furthermore, the ICIS-H group was additionally associated with a longer PFS (p < 0.001) and overall survival (OS; p = 0.001), at significant levels. In the multivariate analysis, both TCIS-H and ICIS-H groups were identified as independent predictors of favorable PFS (p = 0.012 and p = 0.001, respectively). ICIS-H was also shown to be an independent predictor of favorable OS (p = 0.003). The analysis of the mRNA expression data from TCGA also validated our findings regarding TNBC. Conclusion Our novel TCIS and ICIS exhibited a significant prognostic value in TNBC. Additional research would be needed to strengthen our findings and identify the most efficient prognostic and predictive biomarkers for TNBC patients. |
| first_indexed | 2024-03-11T12:37:10Z |
| format | Article |
| id | doaj.art-ffa5e3080264428e9542be9079d001f1 |
| institution | Directory Open Access Journal |
| issn | 1465-542X |
| language | English |
| last_indexed | 2024-03-11T12:37:10Z |
| publishDate | 2023-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Breast Cancer Research |
| spelling | doaj.art-ffa5e3080264428e9542be9079d001f12023-11-05T12:32:57ZengBMCBreast Cancer Research1465-542X2023-11-0125111710.1186/s13058-023-01710-8The prognostic value of a combined immune score in tumor and immune cells assessed by immunohistochemistry in triple-negative breast cancerJi Eun Choi0Jae Seok Lee1Min-Sun Jin2Ilias P. Nikas3Kwangsoo Kim4Sunah Yang5Soo Young Park6Jiwon Koh7Sohyeon Yang8Seock-Ah Im9Han Suk Ryu10Department of Pathology, Chungnam National University Sejong HospitalDepartment of Pathology, Samsung Changwon Hospital, Sungkyunkwan University School of MedicineDepartment of Pathology, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of KoreaSchool of Medicine, European University CyprusTransdisciplinary Department of Medicine and Advanced Technology, Seoul National University HospitalTransdisciplinary Department of Medicine and Advanced Technology, Seoul National University HospitalDepartment of Pathology, Seoul National University College of MedicineDepartment of Pathology, Seoul National University College of MedicineDepartment of Pathology, Seoul National University College of MedicineDepartment of Internal Medicine, Seoul National University Hospital, Seoul National University College of MedicineDepartment of Pathology, Seoul National University College of MedicineAbstract Background This study aimed to develop a novel combined immune score (CIS)-based model assessing prognosis in triple-negative breast cancer (TNBC). Methods The expression of eight immune markers (PD-1, PD-L1, PD-L2, IDO, TIM3, OX40, OX40L, and H7-H2) was assessed with immunohistochemistry on the tumor cells (TCs) and immune cells (ICs) of 227 TNBC cases, respectively, and subsequently associated with selected clinicopathological parameters and survival. Data retrieved from The Cancer Genome Atlas (TCGA) were further examined to validate our findings. Results All immune markers were often expressed in TCs and ICs, except for PD-1 which was not expressed in TCs. In ICs, the expression of all immune markers was positively correlated between one another, except between PD-L1 and OX40, also TIM3 and OX40. In ICs, PD-1, PD-L1, and OX40L positive expression was associated with a longer progression-free survival (PFS; p = 0.040, p = 0.020, and p = 0.020, respectively). In TCs, OX40 positive expression was associated with a shorter PFS (p = 0.025). Subsequently, the TNBC patients were classified into high and low combined immune score groups (CIS-H and CIS-L), based on the expression levels of a selection of biomarkers in TCs (TCIS-H or TCIS-L) and ICs (ICIS-H or ICIS-L). The TCIS-H group was significantly associated with a longer PFS (p < 0.001). Furthermore, the ICIS-H group was additionally associated with a longer PFS (p < 0.001) and overall survival (OS; p = 0.001), at significant levels. In the multivariate analysis, both TCIS-H and ICIS-H groups were identified as independent predictors of favorable PFS (p = 0.012 and p = 0.001, respectively). ICIS-H was also shown to be an independent predictor of favorable OS (p = 0.003). The analysis of the mRNA expression data from TCGA also validated our findings regarding TNBC. Conclusion Our novel TCIS and ICIS exhibited a significant prognostic value in TNBC. Additional research would be needed to strengthen our findings and identify the most efficient prognostic and predictive biomarkers for TNBC patients.https://doi.org/10.1186/s13058-023-01710-8Triple-negative breast cancer (TNBC)Immune checkpoint proteinsPrognostic modelCombined immune scoreProgrammed death ligand 1 (PD-L1)Overall survival (OS) |
| spellingShingle | Ji Eun Choi Jae Seok Lee Min-Sun Jin Ilias P. Nikas Kwangsoo Kim Sunah Yang Soo Young Park Jiwon Koh Sohyeon Yang Seock-Ah Im Han Suk Ryu The prognostic value of a combined immune score in tumor and immune cells assessed by immunohistochemistry in triple-negative breast cancer Breast Cancer Research Triple-negative breast cancer (TNBC) Immune checkpoint proteins Prognostic model Combined immune score Programmed death ligand 1 (PD-L1) Overall survival (OS) |
| title | The prognostic value of a combined immune score in tumor and immune cells assessed by immunohistochemistry in triple-negative breast cancer |
| title_full | The prognostic value of a combined immune score in tumor and immune cells assessed by immunohistochemistry in triple-negative breast cancer |
| title_fullStr | The prognostic value of a combined immune score in tumor and immune cells assessed by immunohistochemistry in triple-negative breast cancer |
| title_full_unstemmed | The prognostic value of a combined immune score in tumor and immune cells assessed by immunohistochemistry in triple-negative breast cancer |
| title_short | The prognostic value of a combined immune score in tumor and immune cells assessed by immunohistochemistry in triple-negative breast cancer |
| title_sort | prognostic value of a combined immune score in tumor and immune cells assessed by immunohistochemistry in triple negative breast cancer |
| topic | Triple-negative breast cancer (TNBC) Immune checkpoint proteins Prognostic model Combined immune score Programmed death ligand 1 (PD-L1) Overall survival (OS) |
| url | https://doi.org/10.1186/s13058-023-01710-8 |
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