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

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.
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https://www.hal.inserm.fr/inserm-03152413
Contributor : Emilie Mamessier <>
Submitted on : Friday, March 12, 2021 - 4:43:55 PM
Last modification on : Tuesday, March 16, 2021 - 3:13:55 AM
Long-term archiving on: : Sunday, June 13, 2021 - 7:14:04 PM

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T Delayre, T Guilbaud, N Resseguier, Emilie Mamessier, M Rubis, et al.. Prognostic impact of tumour-infiltrating lymphocytes and cancer-associated fibroblasts in patients with pancreatic adenocarcinoma of the body and tail undergoing resection. British Journal of Surgery, Wiley, 2020, 107 (6), pp.720-733. ⟨10.1002/bjs.11434⟩. ⟨inserm-03152413⟩

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