Prognostic value of an immune score combining intra- and peritumoral T-cell subset density in patients with pancreatic adenocarcinoma.

Abstract

4060 Background: Immune scoring based on T-cell subsets and density can add prognostic value to conventional TNM staging for patients with solid tumors, but limited data are available for pancreatic adenocarcinoma. Methods: Using tissue microarrays, CD3, CD4, CD8, CD45RO, and FOXP3 T-cells were quantified by immunohistochemistry in the intratumoral (IT) compartment and peritumoral (PT) parenchyma of 111 consecutively resected specimens. T-cell counts were correlated with patient overall survival, disease-free survival, and time to recurrence (OS, DFS, TTR) by Cox regression, controlling for clinicopathological factors. An immune score (IS) based on IT CD4 T-cell count > median, PT CD8 T-cell count ≤ median, and IT/PT CD3 T-cell ratio >1, grouped patients into high, intermediate, or low categories if all 3, 1 to 2, or none of these immune features were present, respectively. Results: Median follow-up time was 20 months, and 85% of patients either died or recurred during the study period. By univariate analysis, PT CD8 T-cell count was associated with shorter OS (p=0.02), whereas both IT CD4 T-cell count and IT/PT CD3 T-cell ratio were associated with longer OS (p=0.01 and p=0.05, respectively). Alone, none of these immune features predicted TTR. Combined into an IS, patients in the high (n=23), intermediate (n=60), or low (n=23) categories had significantly different OS (respective medians 30, 17, and 13 months, log-rank p=0.01), DFS (28, 16, and 12 months, p=0.01), and TTR (21, 14, and 10 months, p=0.02). By multivariate analysis, the association between IS and clinical outcomes was independent of tumor size, extra-pancreatic invasion, and nodal metastases (TNM staging). The IS discriminated outcomes among patients with nodal metastases (n=80), such that node-positive patients with a high IS had a median survival similar to node-negative patients (30 and 33 months, p=0.7). FOXP3 and CD45RO T-cell counts did not appear to add prognostic value to the IS. Conclusions: An immune score that combines specific T-cell location and density may have prognostic value in patients with resected pancreatic adenocarcinoma, independently from pathologic features currently used for staging.