B7 score and T cell infiltration stratify immune status in prostate cancer
Qianghua Zhou1,2, Kaiwen Li1,2, Yiming Lai1,2
1Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
Background:
Although immune checkpoint inhibitors (ICIs), especially programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) axis blockers, exhibit prominent antitumor effects against numerous malignancies, their benefit for patients with prostate cancer (PCa) has been somewhat marginal. This study aimed to assess the feasibility of B7-H3 or HHLA2 as alternative immunotherapeutic targets in PCa.
Methods:
Immunohistochemistry was performed to evaluate the expression pattern of PD-L1, B7-H3 and HHLA2 and the infiltration of CD8+ and Foxp3+ lymphocytes in 239 PCa tissues from two independent cohorts. The correlations between B7-H3 and HHLA2 and clinicopathological features, including the presence of CD8+ and Foxp3+ tumor-infiltrating lymphocytes (TILs), were explored.
Results:
HHLA2 expression was much higher than PD-L1 expression but lower than B7-H3 expression in PCa tissues. High expression of both B7-H3 and HHLA2 was significantly associated with higher Gleason score and tumor stage, lymph node metastasis and dismal overall survival (OS) and cancer-specific survival (CSS). Moreover, a high B7 score, defined as high B7-H3 expression and/or high HHLA2 expression, was an independent prognostic predictor for PCa. Of note, a high B7 score was negatively correlated with CD8+ TILs. Importantly, a new immune classification, based on the B7 score and CD8+ TILs, successfully stratified OS and CSS in PCa.
Conclusions:
Both B7-H3 and HHLA2 have a critical impact on the immunosuppressive microenvironment, and the B7 score could be used as an independent prognostic factor for PCa. The B7 score combined with CD8+ TILs could be used as a new immune classification to stratify the risk of death, especially cancer-related death, for patients with PCa. These findings may provide insights that could improve response to immune-related comprehensive therapy for PCa in the future.
Insights
New targets B7-H3 and HHLA2 show promise for prostate cancer immunotherapy. A combined B7 score and CD8+ T-cell infiltration can predict patient outcomes and guide treatment strategies.
Area of Science:
- Oncology
- Immunology
- Cancer Research
Background:
- Immune checkpoint inhibitors (ICIs) like PD-1/PD-L1 blockers have limited efficacy in prostate cancer (PCa).
- Investigating alternative targets such as B7-H3 and HHLA2 is crucial for advancing PCa immunotherapy.
Purpose of the Study:
- To evaluate B7-H3 and HHLA2 as potential immunotherapeutic targets in prostate cancer.
- To correlate their expression with clinicopathological features and immune cell infiltration.
Main Methods:
- Immunohistochemistry was used to assess PD-L1, B7-H3, and HHLA2 expression in 239 PCa tissues.
- Analysis included CD8+ and Foxp3+ tumor-infiltrating lymphocytes (TILs) and correlation with clinicopathological parameters.
Main Results:
- HHLA2 expression was higher than PD-L1 but lower than B7-H3 in PCa.
- High B7-H3 and HHLA2 expression correlated with advanced disease (Gleason score, stage, nodal metastasis) and poorer survival (OS, CSS).
- A high B7 score (B7-H3 and/or HHLA2) was an independent prognostic predictor and negatively correlated with CD8+ TILs.
Conclusions:
- B7-H3 and HHLA2 significantly impact the immunosuppressive tumor microenvironment in PCa.
- The B7 score serves as a prognostic factor, and its combination with CD8+ TILs offers a novel immune classification for risk stratification.
- These findings may enhance immune-related therapies for prostate cancer.
