Immune checkpoint markers in gastroenteropancreatic neuroendocrine neoplasia

in Endocrine-Related Cancer
Correspondence should be addressed to T Knösel: Thomas.Knoesel@med.uni-muenchen.de
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Cancer immunotherapy has evolved major breakthroughs in the last years. The cell-surface receptor programmed death-1 (PD-1) and its ligand, programmed death ligand-1 (PD-L1), have been detected in various cancer types. However, the analysis on gastroenteropancreatic neoplasia (GEP-NENs) is limited. Therefore, the aim of this study was to characterize GEP-NENs with regard to PD-1/PD-L1 pathway and tumor-infiltrating lymphocytes (TILs). On protein level, we examined TILs, PD-1 and PD-L1 expression in tumor tissue of 244 GEP-NENs using immunohistochemistry. Expression levels were correlated with clinicopathological parameters including long-term survival in an observational study. In total, 244 patients could be included. Most of the patients had a NEN of the small intestine (52.5%) or the pancreas (29.5%). All tumors could be graded by their morphology and Ki67 index, with 57.8% G1, 34% G2 and 8.2% G3 tumors. High TILs (19.6%) and high PD-1 (16.1%) expression showed a significant correlation with shorter patient survival (P < 0.05) and with a higher grading. Furthermore, expression of PD-L1 (8.7%) showed a trend to shorter patient survival. High TILs and PD-1 expression are significantly associated with shorter patient survival and higher grading in GEP-NENs. PD-L1 expression showed a trend to shorter patient survival. Immunotherapy might be a promising therapeutic approach in GEP-NENs especially in tumors with high TILs.

 

      Society for Endocrinology

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    Examples of (A) well-differentiated neuroendocrine tumor (NET, G1), (B) poorly differentiated neuroendocrine carcinoma (NEC, G3) with high TILs and areas of necrosis (10× magnification), (C) high PD-1-positive lymphocytes in specimen with high TILs (40× magnification) and (D) high PD-L1 staining (score 3) in tumor cells within a specimen with high TILs.

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    Kaplan–Meier overall survival curves for patients divided into levels of tumor-infiltrating lymphocytes (TIL) (P < 0.05).

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    Kaplan–Meier overall survival curves for patients with G1/2 (A) (P < 0.05) and G3 (B) tumors (P > 0.05) divided into levels of tumor-infiltrating lymphocytes (TIL).

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    Kaplan–Meier overall survival curves for patients divided into PD-1 expression (P < 0.05).

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    Kaplan–Meier overall survival curves for patients divided into PD-L1 expression (P > 0.05).

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