AACR 2021: Is the B7-H3 Protein an Actionable Target in Prostate Cancer?
Posted: Monday, April 26, 2021
Johann S. De Bono, MD, PhD, of The Institute of Cancer Research, Sutton, United Kingdom, and colleagues studied the longitudinal expression of the B7 family immunomodulatory glycoprotein B7-H3 and its correlation with advanced prostate cancer immunogenomics. It was discovered that membranous B7-H3 is highly expressed in advanced prostate cancer, correlating with low tumor-infiltrating T lymphocytes and BRCA2 and ATM loss of function alterations. These findings, which were presented during the virtual edition of the American Association for Cancer Research (AACR) Annual Meeting 2021 (Abstract LB035), suggest B7-H3 may prove to be a therapeutic target for this disease subset.
The investigators analyzed 141 biopsies, including those of formalin-fixed paraffin-embedded metastatic castration-resistant, treatment-naive, and castration-sensitive prostate cancers. Biopsies were inspected for DNA repair gene alterations, immunohistochemistry, mismatch repair, and the density of tumor-infiltrating T lymphocytes.
A majority of castration-resistant and castration-sensitive prostate cancer biopsies displayed both membranous (95%) and cytoplasmic (97%) B7-H3 expression. As tumors progressed from castration-sensitive to castration-resistant, there appeared to be no significant change in membranous B7-H3 expression (P = .6). Interpatient and intratumor heterogeneity in membranous B7-H3 expression were significant, yet 28.6% of castration-resistant and 32.6% of castration-sensitive tumors had notably high expression.
Membranous B7-H3 expression also seemed to correlate with the existence of deleterious gene alterations that participate in homologous recombination repair, such as BRCA2 mutations and homozygous deletions (P = .0003), as well as ATM loss (P = .001). There was no observed association between membranous B7-H3 expression and defective mismatch repair.
Additionally, there seemed to be an inverse association between membranous B7-H3 expression and the density of intratumor CD3-positive tumor-infiltrating T lymphocytes (P = .004) but no apparent association with stromal tumor-infiltrating T lymphocyte density (P = .4).
Disclosure: For full disclosures of the study authors, visit abstractsonline.com.