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Immune infiltrates and PD-L1 expression in treatment-naïve acinar prostatic adenocarcinoma: an exploratory analysis
Elan Hahn1,2, Stanley K Liu3, Danny Vesprini3
1Anatomic Pathology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
Abstract:
Tumour-induced immunosuppression plays a role in the development and progression of cancer. Of interest is the interaction between programmed death-1 and programmed death ligand-1 (PD-L1) which can be targeted through immune checkpoint blockade; however, there are limited data surrounding the composition of the immune milieu in prostate cancer. We preliminarily assessed 21 radical prostatectomies in therapy-naïve patients for immune markers and PD-L1 expression. The immune infiltrates were higher in adenocarcinoma than benign prostate (lymphocytes p<0.001, macrophages p=0.010) with 5% of cases being PD-L1 high (≥5% expression). Increased peritumoural CD68 and CD163 expression correlated with lower grade group (GG) (p=0.024 and p=0.014, respectively) with a trend towards increased CD68 expression in lower stage cases (p=0.086). There was also increased CD45 expression in lower GGs (p=0.063). We found the immune infiltrate in acinar prostate cancer to be extremely heterogeneous with an overall immunophenotype unlikely to respond to immune checkpoint blockade.
Insights
Prostate cancer immune cells are more abundant in tumors than normal tissue, but PD-L1 expression is low. This suggests limited response to immune checkpoint blockade therapy for most prostate cancer patients.
Area of Science:
- Oncology
- Immunology
- Urology
Background:
- Tumor-induced immunosuppression contributes to cancer progression.
- Programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) interactions are key targets for immune checkpoint blockade.
- Limited data exists on the immune microenvironment in prostate cancer.
Purpose of the Study:
- To assess immune cell infiltrates and PD-L1 expression in therapy-naïve prostate cancer.
- To investigate the relationship between immune markers, PD-L1 expression, and clinicopathological features.
Main Methods:
- Preliminary assessment of 21 radical prostatectomies from therapy-naïve patients.
- Analysis of immune markers (lymphocytes, macrophages, CD68, CD163, CD45) and PD-L1 expression.
- Correlation analysis with prostate cancer grade group (GG) and stage.
Main Results:
- Immune infiltrates (lymphocytes, macrophages) were significantly higher in adenocarcinoma than benign prostate tissue.
- 5% of cases exhibited high PD-L1 expression (≥5%).
- Increased peritumoral CD68 and CD163 expression correlated with lower GG. Increased CD45 expression trended with lower GGs.
- Acinar prostate cancer immune infiltrate was highly heterogeneous.
Conclusions:
- Prostate cancer exhibits a heterogeneous immune microenvironment.
- The overall immunophenotype suggests a limited likelihood of response to current immune checkpoint blockade therapies for most patients.
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