Gustave Roussy, Villejuif, France
Cecile Vicier , Lillian Werner , Ying Huang , Anis Hamid , Carolyn Evan , Massimo Loda , Christopher Sweeney
Background: Given limited information about the prostate cancer (PC) immune infiltrate in men with localized disease, we profiled 6 markers and correlated them with risk of metastases after RP, using a single-institution cohort. Methods: Using a tissue microarray (TMA) with formalin-fixed, paraffin-embedded radical prostatectomy specimens, we performed a multiplex immunohistochemistry (IHC) analysis of immune checkpoint markers (PD1, PDL1), T-cell regulator / helper (FOXP3, CD4) and killer T cells (CD3, CD8). Quantitative multispectral imaging analysis was used to define the “density” of each marker: a ratio between number of positive cells divided by glandular and stromal area. Data collected included patient characteristics, time to biochemical relapse (BCR), time to metastasis (M1) and overall survival (OS). Results: TMA staining resulted data for at least one marker for 129 patients and all 6 markers for 109 patients. Median follow-up for this cohort was 14 years (0.25-27 years). As detailed in the table, either low CD8 or high PDL1 had a statistically significant association with biochemical and metastatic relapse and trend toward poorer OS on univariate analysis (UVA). A risk score of 0, 1 or 2 with CD8 low and PDL1 high each being one point revealed a strong association with higher score and incremental risk of BCR and metastasis. Conclusions: Multiplex IHC profiling of primary prostate cancer revealed high PDL1 and low CD8 density as poor prognostic markers alone and more impactful as part of a risk score for biochemical and metastatic relapse.
Density N = 109 | Time to BCR | Time to metastasis | OS | ||||||
---|---|---|---|---|---|---|---|---|---|
BCR N = 58 | UVA HR (95% CI) | UVA pvalue | M1 N = 39 | UVA HR (95% CI) | UVA pvalue | Deaths N = 32 | UVA HR (95%CI) | UVA pvalue | |
PDL1 | |||||||||
≤med: 55 | 22 | 0.47 (0.27-0.80) | 0.004 | 13 | 0.41 (0.21-0.81) | 0.008 | 13 | 0.66 (0.33-1.34) | 0.25 |
> med: 54 | 36 | 1 | 26 | 1 | 19 | 1 | |||
CD8 | |||||||||
≤med: 63 | 42 | 2.43 (1.36-4.32) | 0.002 | 30 | 2.37 (1.11-5.00) | 0.02 | 26 | 2.20 (0.90-5.43) | 0.08 |
> med: 46 | 16 | 1 | 9 | 1 | 6 | 1 | |||
Score* | |||||||||
0: 253 | 4 | 0.14 (0.05-0.40) | 0.0002 | 1 | 0.07 (0.01-0.49) | 0.003 | 3 | 0.32 (0.09-1.10) | 0.17 |
1: 51 | 30 | 0.78 (0.46-1.33) | 20 | 0.77 (0.40-1.47) | 13 | 0.77 (0.37-1.62) | |||
2: 33 | 24 | 1 | 18 | 1 | 16 | 1 |
* Score 0: high CD8 low PDL1; score 1: high CD8 high PDL1 or low CD8 low PDL1; score 2: low CD8 high PDL1
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