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B7-H3 Expression in Breast Cancer and Brain Metastasis.
Joshi, Vaibhavi; Beecher, Kate; Lim, Malcolm; Stacey, Andrew; Feng, Yufan; Jat, Parmjit S; Duijf, Pascal H G; Simpson, Peter T; Lakhani, Sunil R; McCart Reed, Amy E.
Afiliação
  • Joshi V; UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane 4029, Australia.
  • Beecher K; UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane 4029, Australia.
  • Lim M; UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane 4029, Australia.
  • Stacey A; UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane 4029, Australia.
  • Feng Y; UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane 4029, Australia.
  • Jat PS; MRC Prion Unit at UCL, Institute of Prion Diseases, Courtauld Building, London W1W 7FF, UK.
  • Duijf PHG; Centre for Cancer Biology, Clinical and Health Sciences, University of South Australia & SA Pathology, Adelaide 5001, Australia.
  • Simpson PT; UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane 4029, Australia.
  • Lakhani SR; UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane 4029, Australia.
  • McCart Reed AE; Pathology Queensland, Royal Brisbane and Women's Hospital, Brisbane 4029, Australia.
Int J Mol Sci ; 25(7)2024 Apr 03.
Article em En | MEDLINE | ID: mdl-38612786
ABSTRACT
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Encefálicas / Neoplasias da Mama Limite: Female / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Encefálicas / Neoplasias da Mama Limite: Female / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article