Prognostic impact of tumour-infiltrating lymphocytes and cancer-associated fibroblasts in patients with pancreatic adenocarcinoma of the body and tail undergoing resection. Issue 6 (21st January 2020)

• Record Type: Journal Article
• Authors: Delayre, T; Guilbaud, T; Resseguier, N; Mamessier, E; Rubis, M; Moutardier, V; Fara, R; Berdah, S V; Garcia, S; Birnbaum, D J
• Is Part Of: British journal of surgery. Volume 107:Issue 6(2020)
• Page Start: 720
• Page End: 733
• Publication Date: 2020-01-21
• Subjects: Surgery -- Periodicals; 617.005
• DOI: 10.1002/bjs.11434
• Languages: English
• ISSNs: 0007-1323

Abstract

Abstract: Background: The prognosis of patients with pancreatic cancer remains poor and novel therapeutic targets are required urgently. Treatment resistance could be due to the tumour microenvironment, a desmoplastic stroma consisting of cancer-associated fibroblasts and tumour-infiltrating lymphocytes (TILs). The aim of the study was to evaluate the prognostic value of TILs and cancer-associated fibroblasts (CAFs) in pancreatic cancer of the body and tail. Methods: Using tissue microarray from resected left-sided pancreatic cancer specimens, the immunohistochemistry of TILs (cluster of differentiation (CD) 45, CD3, CD4, FoxP3 and CD8), CAFs (vimentin and α-smooth muscle actin (αSMA)) and functional markers (PD-L1 and Ki-67) was examined, and the association with disease-free (DFS) and overall (OS) survival investigated using a computer-assisted quantitative analysis. Patients were classified into two groups, with low or high levels or ratios, using the 75th percentile value as the cut-off. Results: Forty-three patients were included in the study. Their median DFS and OS were 9 and 27 months respectively. A high CD4/CD3 lymphocyte ratio was associated with poorer DFS (8 months versus 11 months for a low ratio) (hazard ratio (HR) 2·23, 95 per cent c.i. 1·04 to 4·61; P = 0·041) and OS (13 versus 27 months respectively) (HR 2·62, 1·11 to 5·88; P = 0·028). A low αSMA/vimentin ratio together with a high CD4/CD3 ratio was correlated with poorer outcomes. No significant association was found between Ki-67, PD-L1 and survival. Conclusion: In patients with resected left-sided pancreatic cancer, a tumour microenvironment characterized by a high CD4/CD3 lymphocyte ratio along with a low αSMA/vimentin ratio is correlated with poorer survival. Graphical Abstract: To evaluate the prognostic value of tumour-infiltrating lymphocytes (TILs) and cancer-associated fibroblasts (CAFs) in pancreatic ductal adenocarcinoma (PDAC), this study investigated the correlation between lymphocyte infiltration (CD45, CD3, CD4, FoxP3, CD8), CAF expression (vimentin, α-smooth muscle actin (αSMA)) and overall (OS) and disease-free (DFS) survival in patients with resected left-sided PDAC. CD, cluster of differentiation; FoxP3, forkhead box P3; IL, interleukin. Identify patients with the worst prognosis