| Title: |
B7-H3 Expression in Breast Cancer and Brain Metastasis |
| Authors: |
Joshi, Vaibhavi; Beecher, Kate; Lim, Malcolm; Stacey, Andrew; Feng, Yufan; Jat, Parmjit S; Duijf, Pascal HG; Simpson, Peter T; Lakhani, Sunil R; McCart Reed, Amy E |
| Source: |
International Journal of Molecular Sciences , 25 (7) , Article 3976. (2024) |
| Publisher Information: |
MDPI AG |
| Publication Year: |
2024 |
| Collection: |
University College London: UCL Discovery |
| Subject Terms: |
breast cancer; brain metastasis; biomarker; B7-H3; CD276; prognosis; therapeutic target |
| 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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://discovery.ucl.ac.uk/id/eprint/10190937/ |
| Availability: |
https://discovery.ucl.ac.uk/id/eprint/10190937/1/ijms-25-03976.pdf; https://discovery.ucl.ac.uk/id/eprint/10190937/ |
| Rights: |
open |
| Accession Number: |
edsbas.2209FB90 |
| Database: |
BASE |