• Br J Surg · May 2020

    Observational Study

    Prognostic impact of tumour-infiltrating lymphocytes and cancer-associated fibroblasts in patients with pancreatic adenocarcinoma of the body and tail undergoing resection.

    • T Delayre, T Guilbaud, N Resseguier, E Mamessier, M Rubis, V Moutardier, R Fara, S V Berdah, S Garcia, and D J Birnbaum.
    • Digestive and Oncological Surgery Unit, Hôpital Nord, Assistance Publique Hôpitaux de Marseille, Aix-Marseille Université, Faculté de Médecine de Marseille, Chemin des Bourrely, 13915, Marseille Cedex 20, France.
    • Br J Surg. 2020 May 1; 107 (6): 720-733.

    BackgroundThe 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.MethodsUsing 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.ResultsForty-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.ConclusionIn 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.© 2020 BJS Society Ltd Published by John Wiley & Sons Ltd.

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