Objectives Investigation of expression profile of well-established microRNAs in pancreatic adenocarcinoma, and its correlation with clinicopathological factors. Methods Eighty-eight samples of ductal pancreatic adenocarcinoma and 98 control samples were analyzed by real-time polymerase chain reaction for miR-21, miR-31, miR-122, miR-145, miR-146a, miR-155, miR-210, and miR-222 expressions. The results were normalized and then statistically analyzed using nonparametric statistical tests. Results According to our results, miR-21, miR-155, miR-210, miR-221, and miR-222, were overexpressed in diseased tissues than in the control samples, whereas miR-31, miR-122, miR-145, and miR-146a were underexpressed. Additionally, the expressions of miR-21 and miR-155 were associated with tumor stage and poor prognosis. Conclusions The tumorigenic role of miR-21 and miR-155 was confirmed, whereas down-regulation of miR-31, miR-145, and miR-146a, in dispute with current literature, renders necessary the revision of use of microRNAs as biological markers.

The liver is one of the organs most commonly affected by metastasis. The presence of liver metastases has been reported to be responsible for an immunosuppressive microenvironment and diminished immunotherapy efficacy. Herein, we aimed to investigate the role of IL-10 in liver metastasis and to determine how its modulation could affect the efficacy of immunotherapy in vivo. To induce spontaneous or forced liver metastasis in mice, murine cancer cells (MC38) or colon tumor organoids were injected into the cecum or the spleen, respectively. Mice with complete and cell type-specific deletion of IL-10 and IL-10 receptor alpha were used to identify the source and the target of IL-10 during metastasis formation. Programmed death ligand 1 (PD-L1)-deficient mice were used to test the role of this checkpoint. Flow cytometry was applied to characterize the regulation of PD-L1 by IL-10. We found that Il10-deficient mice and mice treated with IL-10 receptor alpha antibodies were protected against liver metastasis formation. Furthermore, by using IL-10 reporter mice, we demonstrated that Foxp3+ regulatory T cells (Tregs) were the major cellular source of IL-10 in liver metastatic sites. Accordingly, deletion of IL-10 in Tregs, but not in myeloid cells, led to reduced liver metastasis. Mechanistically, IL-10 acted on Tregs in an autocrine manner, thereby further amplifying IL-10 production. Furthermore, IL-10 acted on myeloid cells, i.e. monocytes, and induced the upregulation of the immune checkpoint protein PD-L1. Finally, the PD-L1/PD-1 axis attenuated CD8-dependent cytotoxicity against metastatic lesions. Treg-derived IL-10 upregulates PD-L1 expression in monocytes, which in turn reduces CD8+ T-cell infiltration and related antitumor immunity in the context of colorectal cancer-derived liver metastases. These findings provide the basis for future monitoring and targeting of IL-10 in colorectal cancer-derived liver metastases. Liver metastasis diminishes the effectiveness of immunotherapy and increases the mortality rate in patients with colorectal cancer. We investigated the role of IL-10 in liver metastasis formation and assessed its impact on the effectiveness of immunotherapy. Our data show that IL-10 is a pro-metastatic factor involved in liver metastasis formation and that it acts as a regulator of PD-L1. This provides the basis for future monitoring and targeting of IL-10 in colorectal cancer-derived liver metastasis.

MicroRNAs are molecules implicated in RNA-RNA interaction, playing a role in cell proliferation and differentiation, as well as in carcinogenesis. Knowledge on their biological features is necessary to understand their role in phenotypic characteristics of pancreatic adenocarcinoma. Review of current literature concerning mechanisms of action, studying methods, implementations, and preclinical trials on pancreatic adenocarcinoma. More than 20 microRNAs have been identified, being involved in pancreatic adenocarcinoma biology, affecting tumor growth, metastatic potential, and chemosensitivity. Combinations of microRNAs can be used to differentiate between pancreatic adenocarcinoma and other pancreatic pathologies, as well as to assess prognosis. Manipulations of microRNAs can decrease the rate of growth or reinstall chemosensitivity to certain chemotherapeutic agents. The field of microRNAs promises novel diagnostic and therapeutic tools in the management of pancreatic adenocarcinoma.

Background: Sentinel lymph node (SLN) biopsy is the standard of care for breast cancer patients with non-palpable axillary lymph nodes. We evaluated the usefulness of contrast-enhanced ultrasonography in preoperative detection of malignant SLNs. Methods: 50 patients with breast cancer (median age: 60 years) underwent a color power Doppler ultrasonography with intravenous contrast (Sonovue®) preoperatively, and findings suggestive of metastatic disease to the SLN were documented. The final histopathological report and the radiological preoperative record were compared. Finally, the sensitivity, specificity and diagnostic accuracy of this evolving diagnostic modality were calculated. Results: Contrast-enhanced ultrasound scan identified a negative SLN in the axilla of 27 patients and final histopathology was negative for 30 cases in total, so negative predictive value was calculated as 90% and positive predictive value was 75%. Overall sensitivity was 83.33% and specificity was 84.38%. Moreover, the ability of contrast-enhanced ultrasound to differentiate between SLN status was only statistically significantly correlated with the actual final histopathological report (p < 0.001), while successful ultrasound prediction was not correlated with any factor. Conclusions: SLN status can be evaluated preoperatively using contrast-enhanced color Doppler ultrasonography with high accuracy.