Le système immunitaire et le stroma tumoral jouent-ils un rôle pronostique dans l'adénocarcinome pancréatique

Abstract : Background: Pancreatic ductal adenocarcinoma (PDAC) prognosis remains poor and novel therapeutic targets are urgently required. Treatment resistance could be imputable to the tumor microenvironment, a desmoplastic stroma composed by cancer-associated fibroblasts (CAFs) associated with tumor-infiltrating lymphocytes (TILs). The aim of the study was to evaluate the prognostic value of TILs and CAFs in resected left-sided PDAC patients. Methods: Using tissue micro-array (TMA), we performed immunohistochemistry of TILs (CD45, CD3, CD4, FoxP3 and CD8), CAFs (vimentin and alpha-smooth muscle actin (αSMA)) and functional markers (PD-L1 and Ki67) on left-sided PDAC specimens, and investigated their association with disease-free survival (DFS) and overall survival (OS). Results were obtained with a computer-assisted quantitative analysis. Patients were classified into two groups, low and high, using 75th percentile value as the cut-off. Results: Forty-three patients were included in the study. In this population, median DFS and OS were 9 months and 16 months respectively. A high CD4/CD3 lymphocytes ratio was associated with poorer DFS and OS (8 months (p=0.04) and 13 months (p =0.03) respectively). A low αSMA/vimentin ratio along with a high CD4/CD3 ratio was also correlated with poorer outcomes. No significant association was found between Ki67, PDL1 and survival. Conclusion: Tumor microenvironment characterized by a high CD4/CD3 lymphocytes ratio along with a low αSMA/vimentin ratio represents a prognostic factor associated with poorer survival in resected left-sided PDAC patients.
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Submitted on : Thursday, July 4, 2019 - 3:21:42 PM
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Thomas Delayre. Le système immunitaire et le stroma tumoral jouent-ils un rôle pronostique dans l'adénocarcinome pancréatique. Sciences du Vivant [q-bio]. 2019. ⟨dumas-02173571⟩

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