Downstream Signaling of Inflammasome Pathway Affects Patients’ Outcome in the Context of Distinct Molecular Breast Cancer Subtypes

Inflammasomes are protein complexes involved in the regulation of different biological conditions. Over the past few years, the role of NLRP3 in different tumor types has gained interest. In breast cancer (BC), NLRP3 has been associated with multiple processes including epithelia mesenchymal transition, invasion and metastization. Little is known about molecular modifications of NLRP3 up-regulation. In this study, in a cohort of BCs, the expression levels of NLRP3 and PYCARD were analyzed in combination with CyclinD1 and MYC ones and their gene alterations. We described a correlation between the NLRP3/PYCARD axis and CyclinD1 (p < 0.0001). NLRP3, PYCARD and CyclinD1’s positive expression was observed in estrogen receptor (ER) and progesterone receptor (PgR) positive cases (p < 0.0001). Furthermore, a reduction of NLRP3 and PYCARD expression has been observed in triple negative breast cancers (TNBCs) with respect to the Luminal phenotypes (p = 0.017 and p = 0.0015, respectively). The association NLRP3+/CCND1+ or PYCARD+/CCND1+ was related to more aggressive clinicopathological characteristics and a worse clinical outcome, both for progression free survival (PFS) and overall survival (OS) with respect to NLRP3+/CCND1− or PYCARD+/CCND1− patients, both in the whole cohort and also in the subset of Luminal tumors. In conclusion, our study shows that the NLRP3 inflammasome complex is down-regulated in TNBC compared to the Luminal subgroup. Moreover, the expression levels of NLRP3 and PYCARD together with the alterations of CCND1 results in Luminal subtype BC’ss poor prognosis

PD-L1 and Notch as novel biomarkers in Pancreatic Sarcomatoid Carcinoma: a pilot study

Background: The improved immunological understanding revealed the tumor microenvironment as an appealing driver to restore the immune response against cancer cells resulting in a paradigm shift in the oncology field. However, the complexity of the tumor milieu suggests a role of several pathways linking in immunomodulation mechanisms. Pancreatic cancer represents a model of the intricate relationship between malignant cells and their surrounding neighborhood. Research design and methods: In this study we analyzed, retrospectively, 6 cases of rare pancreatic sarcomatoid carcinoma (PSC) and evaluated the expression of PD-L1 and Notch, aiming to explore new attributes in immunophenotype. Results: PD-L1 CPS≥1% was common in PSCs (83%) with half samples expressing PD-L1 CPS≥50%. Notch1 and Notch3 expression resulted positive demonstrating a high IRS range of expression. A direct significant correlation between PD-L1 and Nocth3 overexpression (r=0.7; p=0.036) has been observed. Moreover, immunofluorescence studies revealed a co-localization of Notch3 and PD-L1 when both proteins were over-expressed within cytoplasmic or membranous compartments of the same cells. Conclusions: Our data identify a unique biological characterization of this rare pancreatic histotype. These findings provide a rationale for future studies evaluating the potential crosstalk between PD-L1/PD-1 axis and Notch pathways and prompting the development of novel therapeutics strategy