ArticleMolecular medicine (Cambridge, Mass.)2026
Prognostic significance and tumor cell interactions of tumor-associated neutrophils in gastric cancer.
Article in Molecular medicine (Cambridge, Mass.), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundThis study aimed to determine the clinicopathologic implications and tumor cell interaction of CD66b-positive (CD66b +) tumor-associated neutrophils (TANs) and CD66b and CD177 double positive (CD66b + /CD177 +) activated TANs in gastric cancer (GC).
methodsSingle immunohistochemistry (sIHC) for CD66b, CD8, HER2, p53, and E-cadherin was performed in 1,060 patients with GC, together with microsatellite instability (MSI) testing and Epstein-Barr virus (EBV) in situ hybridization. Opal multiplex immunofluorescence (mIF) for cytokeratin (CK), CD66b, and CD177, and sIHC for ERα was performed on 59 microsatellite-stable (MSS) and 60 MSI-high (MSI-H) GCs. The immune cell densities were quantified using QuPath for sIHC and InForm for mIF.
resultsOn sIHC, a high density of CD66b + TANs was correlated with HER2 positivity, EBV positivity, and MSI-H phenotype (p < 0.001). Combined analysis of CD66b + TAN densities in the tumor center and invasive margin showed a significant association with better OS (p = 0.036), independent of major clinicopathologic factors. TAN densities were significantly associated with OS in female patients (p < 0.001), but not in male patients (p = 0.574). The density of ERα-positive immune cells was inversely correlated with TAN density (ρ = -0.41, p < 0.001). mIF analysis demonstrated that both CD66b + TANs and CD66b + /CD177 + activated TANs were significantly more abundant in MSI-H GC than in MSS GC. Moreover, the distance between TANs and CK + GC cells was significantly shorter in MSI-H GC than in MSS GC. A shorter distance between CD66b + /CD177 + activated TANs and GC cells was also associated with a better OS (p = 0.041).
conclusionA high TAN density in GC is associated with a favorable prognosis, and the spatial proximity of TANs to GC cells, especially in MSI-H GC, provides additional prognostic value. These findings provide basic knowledge for the development of therapeutic targets related to TANs in GC.
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