B7-H3 Expression in Breast Cancer and Brain Metastasis
Brain metastasis is a significant challenge for some breast cancer patients, marked by its aggressive nature, limited treatment options, and poor clinical outcomes. Immunotherapies have emerged as a promising avenue for brain metastasis treatment. B7-H3 (CD276) is an immune checkpoint molecule invol...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/7/3976 |
| _version_ | 1797212462407221248 |
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| author | Vaibhavi Joshi Kate Beecher Malcolm Lim Andrew Stacey Yufan Feng Parmjit S. Jat Pascal H. G. Duijf Peter T. Simpson Sunil R. Lakhani Amy E. McCart Reed |
| author_facet | Vaibhavi Joshi Kate Beecher Malcolm Lim Andrew Stacey Yufan Feng Parmjit S. Jat Pascal H. G. Duijf Peter T. Simpson Sunil R. Lakhani Amy E. McCart Reed |
| author_sort | Vaibhavi Joshi |
| collection | DOAJ |
| description | Brain metastasis is a significant challenge for some breast cancer patients, marked by its aggressive nature, limited treatment options, and poor clinical outcomes. Immunotherapies have emerged as a promising avenue for brain metastasis treatment. B7-H3 (CD276) is an immune checkpoint molecule involved in T cell suppression, which is associated with poor survival in cancer patients. Given the increasing number of clinical trials using B7-H3 targeting CAR T cell therapies, we examined B7-H3 expression across breast cancer subtypes and in breast cancer brain metastases to assess its potential as an interventional target. B7-H3 expression was investigated using immunohistochemistry on tissue microarrays of three clinical cohorts: (i) unselected primary breast cancers (n = 347); (ii) brain metastatic breast cancers (n = 61) and breast cancer brain metastases (n = 80, including a subset of 53 patient-matched breast and brain metastasis cases); and (iii) mixed brain metastases from a range of primary tumours (n = 137). In primary breast cancers, B7-H3 expression significantly correlated with higher tumour grades and aggressive breast cancer subtypes, as well as poorer 5-year survival outcomes. Subcellular localisation of B7-H3 impacted breast cancer-specific survival, with cytoplasmic staining also correlating with a poorer outcome. Its expression was frequently detected in brain metastases from breast cancers, with up to 90% expressing B7-H3. However, not all brain metastases showed high levels of expression, with those from colorectal and renal tumours showing a low frequency of B7-H3 expression (0/14 and 2/16, respectively). The prevalence of B7-H3 expression in breast cancers and breast cancer brain metastases indicates potential opportunities for B7-H3 targeted therapies in breast cancer management. |
| first_indexed | 2024-04-24T10:42:46Z |
| format | Article |
| id | doaj.art-e39012a2f4b9493e998e2db87a5a4b85 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-04-24T10:42:46Z |
| publishDate | 2024-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e39012a2f4b9493e998e2db87a5a4b852024-04-12T13:20:17ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-04-01257397610.3390/ijms25073976B7-H3 Expression in Breast Cancer and Brain MetastasisVaibhavi Joshi0Kate Beecher1Malcolm Lim2Andrew Stacey3Yufan Feng4Parmjit S. Jat5Pascal H. G. Duijf6Peter T. Simpson7Sunil R. Lakhani8Amy E. McCart Reed9UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane 4029, AustraliaUQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane 4029, AustraliaUQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane 4029, AustraliaUQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane 4029, AustraliaUQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane 4029, AustraliaMRC Prion Unit at UCL, Institute of Prion Diseases, Courtauld Building, London W1W 7FF, UKCentre for Cancer Biology, Clinical and Health Sciences, University of South Australia & SA Pathology, Adelaide 5001, AustraliaUQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane 4029, AustraliaUQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane 4029, AustraliaUQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane 4029, AustraliaBrain metastasis is a significant challenge for some breast cancer patients, marked by its aggressive nature, limited treatment options, and poor clinical outcomes. Immunotherapies have emerged as a promising avenue for brain metastasis treatment. B7-H3 (CD276) is an immune checkpoint molecule involved in T cell suppression, which is associated with poor survival in cancer patients. Given the increasing number of clinical trials using B7-H3 targeting CAR T cell therapies, we examined B7-H3 expression across breast cancer subtypes and in breast cancer brain metastases to assess its potential as an interventional target. B7-H3 expression was investigated using immunohistochemistry on tissue microarrays of three clinical cohorts: (i) unselected primary breast cancers (n = 347); (ii) brain metastatic breast cancers (n = 61) and breast cancer brain metastases (n = 80, including a subset of 53 patient-matched breast and brain metastasis cases); and (iii) mixed brain metastases from a range of primary tumours (n = 137). In primary breast cancers, B7-H3 expression significantly correlated with higher tumour grades and aggressive breast cancer subtypes, as well as poorer 5-year survival outcomes. Subcellular localisation of B7-H3 impacted breast cancer-specific survival, with cytoplasmic staining also correlating with a poorer outcome. Its expression was frequently detected in brain metastases from breast cancers, with up to 90% expressing B7-H3. However, not all brain metastases showed high levels of expression, with those from colorectal and renal tumours showing a low frequency of B7-H3 expression (0/14 and 2/16, respectively). The prevalence of B7-H3 expression in breast cancers and breast cancer brain metastases indicates potential opportunities for B7-H3 targeted therapies in breast cancer management.https://www.mdpi.com/1422-0067/25/7/3976breast cancerbrain metastasisbiomarkerB7-H3CD276prognosis |
| spellingShingle | Vaibhavi Joshi Kate Beecher Malcolm Lim Andrew Stacey Yufan Feng Parmjit S. Jat Pascal H. G. Duijf Peter T. Simpson Sunil R. Lakhani Amy E. McCart Reed B7-H3 Expression in Breast Cancer and Brain Metastasis International Journal of Molecular Sciences breast cancer brain metastasis biomarker B7-H3 CD276 prognosis |
| title | B7-H3 Expression in Breast Cancer and Brain Metastasis |
| title_full | B7-H3 Expression in Breast Cancer and Brain Metastasis |
| title_fullStr | B7-H3 Expression in Breast Cancer and Brain Metastasis |
| title_full_unstemmed | B7-H3 Expression in Breast Cancer and Brain Metastasis |
| title_short | B7-H3 Expression in Breast Cancer and Brain Metastasis |
| title_sort | b7 h3 expression in breast cancer and brain metastasis |
| topic | breast cancer brain metastasis biomarker B7-H3 CD276 prognosis |
| url | https://www.mdpi.com/1422-0067/25/7/3976 |
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