Intratumor Microbiome in Neuroendocrine Neoplasms: A New Partner of Tumor Microenvironment? A Pilot Study

Abstract

Neuroendocrine neoplasms (NENs) are rare neoplasms with heterogeneous clinical behavior. Alteration in human microbiota was reported in association with carcinogenesis in different solid tumors. However, few studies addressed the role of microbiota in NEN. We here aimed at evaluating the presence of bacterial infiltration in neuroendocrine tumoral tissue. To assess the presence of bacteria, 20 specimens from pancreatic NEN (pan-NEN) and 20 from intestinal NEN (I-NEN) were evaluated through Fluorescent In situ Hybridization and confocal microscopy. Demographic data, pre-operative investigations, operative findings, pathological diagnosis, follow-up, and survival data were evaluated. Among I-NEN, bacteria were detected in 15/20 (75%) specimens, with high variability in microbial distribution. In eight patients, a high infiltration of microorganisms was observed. Among pan-NEN, 18/20 (90%) showed microorganisms’ infiltration, with a homogeneous microbial distribution. Bacterial localization in pan-NEN was observed in the proximity of blood vessels. A higher bacterial infiltration in the tumoral specimen as compared with non-tumoral tissue was reported in 10/20 pan-NEN (50%). No significant differences were observed in mean bacterial count according to age, sex, ki67%, site, tumor stage. Mean bacterial count did not result to be a predictor of disease-specific survival. This preliminary study demonstrates the presence of a significant microbiota in the NEN microenvironment. Further research is needed to investigate the potential etiological or clinical role of microbiota in NEN.

Defining Tumor Microenvironment as a Possible Target for Effective GEP-NENs Immunotherapy—A Systematic Review

“…In the intestine, the distribution varied, yet in the pancreas, bacteria were found mainly in the proximity of blood vessels. However, no statistically significant differences were observed in mean bacterial count according to patients' age, sex, ki 67% index, site, or tumor stage [72]. In conclusion, bacterial colonization has not been confirmed as a prognostic marker or pivotal player in tumor progression.…”

Involvement of the Gut Microbiome in the Local and Systemic Immune Response to Pancreatic Ductal Adenocarcinoma

“…Breast and pancreatic tumours have been shown to have a particularly diverse microbiome [ 64 ]. Notably, the composition of the PDAC tumour microbiome has been associated with prognosis [ 21 , 23 ], which is similar to other gastrointestinal tumour types such as cholangiocarcinoma [ 65 ], neuroendocrine [ 66 ] and colorectal cancers [ 67 , 68 ]. In pancreatic cancer, distinct microbial communities have been identified within tumour areas compared to adjacent pancreatic tissues [ 21 , 23 , 64 , 69 ].…”

Dysbiosis Signature of Fecal Microbiota in Patients with Pancreatic Adenocarcinoma and Pancreatic Intraductal Papillary Mucinous Neoplasms

“…The fecal microbiome offers the advantage of being easily accessible without the need for any invasive procedure, while it is currently widely accepted that it is involved in tumorigenesis of various cancers, including pancreatic [22,23] and distant bile ductal [24], which share developmental origins. Microbiome signatures have already shown promising results in the early diagnosis of cancers, including hepatocellular carcinoma [25] and colorectal cancer [26,27] and simpler pancreatic condition like pancreatitis [28]. More importantly, the fecal microbiome has been already found to play a role in the development of malignancies from precursor lesions, as in the case of colorectal cancer development from polyps [29].…”