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- Title
Tumor-Infiltrating Neutrophils Predict Poor Survival of Non-Functional Pancreatic Neuroendocrine Tumor.
- Authors
Zhang, Wu-Hu; Wang, Wen-Quan; Gao, He-Li; Xu, Shuai-Shuai; Li, Shuo; Li, Tian-Jiao; Han, Xuan; Xu, Hua-Xiang; Li, Hao; Jiang, Wang; Ye, Long-Yun; Lin, Xuan; Wu, Chun-Tao; Yu, Xian-Jun; Liu, Liang
- Abstract
<bold>Objective: </bold>This study retrospectively characterized the immune infiltrating profile in nonfunctional pancreatic neuroendocrine tumors (NF-PanNETs).<bold>Methods: </bold>Tumor tissues from the 109-patient Fudan cohort and a 73-patient external validation set were evaluated by immunohistochemistry for 9 immune cell types: tumor-infiltrating neutrophils (TINs), tumor-associated macrophages (TAMs), CD11c+ dendritic cells, anti-NCR1+ natural killer (NK) cells, CD4+ and CD8+ T cells, CD45RO+ memory T cells, FOXP3+ regulatory T cells (Tregs), and CD20+ B cells.<bold>Results: </bold>TINs were primarily distributed in the intratumoral area, dendritic cells and NK cells were scattered evenly in intratumoral and stromal areas, and Tregs were rarely detected. The remaining 5 cell types were primarily present in peritumoral stroma. Total TINs (P < .001) and TAMs (P = .002) increased as NF-PanNET grade rose. Kaplan-Meier analyses showed that high intratumoral TINs, total TAMs, and stromal CD4+ T-cell infiltration correlated with shorter recurrence-free survival (RFS, P = .010, P = .027, and P = .035, respectively) and overall survival (OS, P = .017, P = .029, and P = .045, respectively). Additionally, high intratumoral CD8+ T cell infiltration correlated with prolonged RFS (P = .039). Multivariate Cox regression demonstrated that intratumoral TINs, World Health Organization (WHO) classification, and eighth edition of the American Joint Committee on Cancer tumor-node-metastasis staging system (AJCC8th TNM) were independent factors for RFS (P = .043, P = .023, and P = .029, respectively), whereas intratumoral TINs and WHO classification were independent factors for OS (P = .010 and P = .007, respectively). Furthermore, the combination of TINs, WHO classification, and AJCC8th TNM remarkably improved prognostic accuracy for RFS. These results have been verified in the external validation set.<bold>Conclusion: </bold>Intratumoral TINs are an independent and unfavorable predictor of postoperative NF-PanNETs. A combination of TINs, WHO classification, and AJCC8th TNM could improve prognostic accuracy for RFS.
- Subjects
PANCREATIC tumors; NEUROENDOCRINE tumors; KILLER cells; SUPPRESSOR cells; T cells; NEUTROPHILS; SURGICAL enucleation; RESEARCH; RESEARCH methodology; RETROSPECTIVE studies; PROGNOSIS; EVALUATION research; MEDICAL cooperation; COMPARATIVE studies
- Publication
Journal of Clinical Endocrinology & Metabolism, 2020, pN.PAG
- ISSN
0021-972X
- Publication type
journal article
- DOI
10.1210/clinem/dgaa196