: Intraductal oncocytic papillary neoplasm (IOPN) of the pancreas is a distinct entity from intraductal papillary mucinous neoplasms (IPMNs) and is considered one of the precursor lesions of pancreatic cancer. Through immunohistochemistry (IHC) and an artificial intelligence (AI)-based approach, this study aims at characterizing its immune microenvironment. Whole-slide IHC was performed on a cohort of 15 IOPNs, 2 of which harboring an associated adenocarcinoma. The following markers were tested: CD3, CD4, CD8, CD20, CD68, CD163, PD-1, PD-L1, MLH1, PMS2, MSH2, and MSH6. The main findings can be summarized as follows: (i) CD8+ T lymphocytes were the predominant immune cells (p < 0.01); (ii) the vast majority of macrophages were concurrently CD68+ and CD163+; (iii) all tumors showed an activated PD-1/PD-L1 axis, but none had mismatch repair deficiency; (iv) AI-based analysis revealed the presence of 2 distinct regions in each case, namely, Re1, localized at the center of the tumor, and Re2, located at tumor periphery; (v) the infiltrating component of the 2 invasive IOPNs showed a smaller extent of Re1 and a reduced rate of CD4+ cells, as well as a larger extent of Re2 and increased rate of CD8+ cells. IOPNs are lesions enriched in immune cells, with a predominance of CD8+ T lymphocytes and class 2 macrophages. Differently from IPMN-oncogenesis, the progression towards invasive carcinoma is accompanied by an increased rate of CD8+ lymphocytes. This finding may suggest the presence of an active self-immune surveillance in invasive IOPNs, potentially explaining, at least in part, the excellent survival rate of IOPN patients.

Characterization and digital spatial deconvolution of the immune microenvironment of intraductal oncocytic papillary neoplasms (IOPN) of the pancreas

Pea, Antonio;Paolino, Gaetano;Martelli, Filippo;Bariani, Elena;Sereni, Elisabetta;Salvia, Roberto;Lawlor, Rita T;Scarpa, Aldo;Luchini, Claudio
2023-01-01

Abstract

: Intraductal oncocytic papillary neoplasm (IOPN) of the pancreas is a distinct entity from intraductal papillary mucinous neoplasms (IPMNs) and is considered one of the precursor lesions of pancreatic cancer. Through immunohistochemistry (IHC) and an artificial intelligence (AI)-based approach, this study aims at characterizing its immune microenvironment. Whole-slide IHC was performed on a cohort of 15 IOPNs, 2 of which harboring an associated adenocarcinoma. The following markers were tested: CD3, CD4, CD8, CD20, CD68, CD163, PD-1, PD-L1, MLH1, PMS2, MSH2, and MSH6. The main findings can be summarized as follows: (i) CD8+ T lymphocytes were the predominant immune cells (p < 0.01); (ii) the vast majority of macrophages were concurrently CD68+ and CD163+; (iii) all tumors showed an activated PD-1/PD-L1 axis, but none had mismatch repair deficiency; (iv) AI-based analysis revealed the presence of 2 distinct regions in each case, namely, Re1, localized at the center of the tumor, and Re2, located at tumor periphery; (v) the infiltrating component of the 2 invasive IOPNs showed a smaller extent of Re1 and a reduced rate of CD4+ cells, as well as a larger extent of Re2 and increased rate of CD8+ cells. IOPNs are lesions enriched in immune cells, with a predominance of CD8+ T lymphocytes and class 2 macrophages. Differently from IPMN-oncogenesis, the progression towards invasive carcinoma is accompanied by an increased rate of CD8+ lymphocytes. This finding may suggest the presence of an active self-immune surveillance in invasive IOPNs, potentially explaining, at least in part, the excellent survival rate of IOPN patients.
2023
Artificial intelligence; Digital pathology; IOPN; IPMN; Oncocytic; TME
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/1092687
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