Tumor-infiltrating neutrophils in pancreatic neoplasia

Abstract

The interaction between tumor cells and inflammatory cells has an important role in cancer initiation and progression; however, this interaction has not been systematically investigated in pancreatic neoplasia. In this study, the presence of tumor-infiltrating neutrophils within and/or adjacent to neoplastic cells was investigated in pancreatic neoplasms. Areas with >10 tumor-infiltrating neutrophils/100 epithelial cells were arbitrarily classified as positive. Those with 11–15 tumor-infiltrating neutrophils were considered ‘borderline’ while those with >15 tumor-infiltrating neutrophils were considered ‘significant’. Among 363 invasive ductal carcinomas, 15 showed significant tumor-infiltrating neutrophils (8 were micropapillary carcinomas and 7 were undifferentiated carcinomas). Of 19 mucinous cystic neoplasms with a carcinomatous high-grade papillary component, 11 showed significant tumor-infiltrating neutrophils (mean, 25; range, 14–63 tumor-infiltrating neutrophils). Among intraductal papillary mucinous neoplasms, significant tumor-infiltrating neutrophils were identified in 4/16 pancreatobiliary type, but were uncommon in other types (1/11 oncocytic and 1/23 intestinal types had borderline tumor-infiltrating neutrophils, and 0/10 gastric type had tumor-infiltrating neutrophils). Non-carcinomatous (low-grade and non-papillary) components of these neoplasms did not have tumor-infiltrating neutrophils. Tumor-infiltrating neutrophils were not striking in neuroendocrine tumors (40), serous cystadenomas (18), acinar cell carcinomas (9) or solid-pseudopapillary neoplasms (8). In conclusion, significant tumor-infiltrating neutrophils are uncommon in pancreatic ductal adenocarcinoma, and when they occur it is typically in the micropapillary and undifferentiated types with a known poor prognosis. Among pre-invasive neoplasia, tumor-infiltrating neutrophils show a predilection for papillary in-situ carcinomas of mucinous cystic neoplasms, or less commonly, pancreatobiliary-type intraductal papillary mucinous neoplasms (both of which express cell surface-associated mucin 1 (MUC1)). MUC1 expression by these tumors may have biologic implications, considering its recently established relationship with inflammatory cells in carcinogenesis, and the differential expression of mucins in pancreatic neoplasia. Larger studies are needed to investigate the association between tumor-infiltrating neutrophils and pancreatic neoplasms and their role in their clinical behavior.

Delayed apoptosis of tumor associated neutrophils in the absence of endogenous IFN‐β

“…32 Similarly, infiltration of gliomas by neutrophils has been correlated with higher tumor stages 33 and it is apparently also associated with more aggressive types of pancreas carcinomas. 34 In accordance, tumor infiltrating neutrophils represent a highly potent therapeutic target. Thus, to understand the physiology of tumor infiltrating neutrophils is of utmost importance.…”

The Multifaceted Roles Neutrophils Play in the Tumor Microenvironment

“…However, neutrophils are also actively recruited into the tumor microenvironment in both cancer patients and mouse models of cancer. In humans, intratumoral infiltration of neutrophils has been detected in gastric carcinoma [200][201][202], bronchioloalveolar carcinoma [170,203], non-small cell lung carcinoma [204], pancreatic neoplasia [205], pancreatic ductal adenocarcinoma [206], bladder cancer [147], glioma [207], cervical carcinoma [139] and breast carcinoma [4,208] ( Table 1). The clinical consequences of intratumoral and circulating neutrophils in cancer patients will be discussed in "Prognostic Values of Neutrophils and Other Myeloid Subtypes in Cancer Patients" section.…”

Updates and Critical Evaluation on Novel Biomarkers for the Malignant Progression of Intraductal Papillary Mucinous Neoplasms of the Pancreas

“…Another study showed that pancreatic adenocarcinoma-infiltrating γδ-T cells are a highly influential lymphocyte subset promoting pancreatic oncogenesis and reducing survival via novel cross-talk with the adaptive immune compartment; Nevertheless, they may also have prognostic significance of survival and response to immunotherapeutic regimen (77). Investigators from our Institution have reported an association between tumorassociated neutrophils (TANs) and advanced IPMN lesions (78). The recent publication of Gemenetzis et al (79) evaluating the correlation between NLR and platelet-tolymphocyte ratio (PLR) values and the presence of invasive carcinoma in patients with IPMN.…”