Tumor-Associated Macrophages: toward a better understanding of their cancer driver capability in Malignant Pleural Mesothelioma

Malignant Pleural Mesothelioma (MPM) is an aggressive cancer of the serosal cavities, characterized by a non-resolving, long-lasting inflammation driven by the presence of non-degradable asbestos fibers. MPM is strongly related to professional or environmental exposure to airborne asbestos. About 1400 new cases/year are observed in Italy, and its peak incidence is estimated around 2020- 2025. Chronic inflammation, eventually causing irreversible DNA damage, has been established as the main pa...

Single Cell Sequencing approach for defining cardioinflammatory mechanisms driving Heart Failure with Preserved Ejection Fraction in metabolic stress

Molecular characterization of cellular heterogeneity in pancreatic ductal adenocarcinoma by transcriptome profiling

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with an extremely aggressive behavior due to both the advanced stage of the disease at diagnosis and the peculiar biology of this tumor. The current classifications of PDAC in different subtypes failed to associate defined molecular properties with specific morphological features and disease outcomes, thus making the histopathological classification of PDAC not informative for patient stratification for therapy choice. In order to pr...

IMPACT OF EARLY DISEASE CLEARANCE ON LONG-TERM OUTCOMES IN ULCERATIVE COLITIS: A MULTICENTER COHORT STUDY

Background: Clinical remission and endoscopic mucosal healing are the main treatment targets in patients with ulcerative colitis (UC). Recently, the concept of disease clearance has been proposed as a potential target in UC. Aim: To evaluate the impact of disease clearance on long-term outcomes in UC patients. Methods: A multicenter retrospective cohort study was conducted at the Humanitas Research Hospital-IRCCS (Italy) and at the Nancy University Hospital (France). Disease clearance wa...

Parkinson’s disease: understanding disease pathogenesis by different model systems

Parkinson Disease (PD) is a neurodegenerative disease caused by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta and characterized by resting tremor, bradykinesia, rigidity, and postural instability. PD is a complex disease caused by the combination of environmental and genetic determinants. In the last 20 years considerable progresses have been made in the identification of the genetic components of PD: different genes were shown to cause rare monogenic form...

Genome-wide characterisation of clinical kinase inhibitors in macrophage activation.

The possibility to control kinase activities through the use of chemical inhibitors is a key strategy for the treatment of numerous pathologies. To date, 243 kinase inhibitors are in clinical trials and of these 62 are approved by the FDA. Frequently, kinase inhibitors are designed on the basis of conserved features of the kinase domain. Although this approach proved to be highly effective, it also leads to the common occurrence of off-target effects. So far, the impact of kinase inhibitors o...

Characterization of a population of innate like T cells in mouse and human

T lymphocytes expressing a mature TCRαβ are classified in conventional T cells (CD4+ and CD8+) and unconventional T cells (UTCs), including invariant natural killer T cells (iNKT), mucosal-associated invariant T cells (MAIT) and intraepithelial lymphocytes (IELs). Our group recently identified a poorly defined population of UTCs referred to as double-negative αβ T cells (DNTαβ) and involved in resistance against sarcoma. DNTαβ express a TCRαβ but are not recognized by antigen-loaded CD1d tetr...

Sensitizing tumor cells to immunotherapy by postbiotic-mediated upregulation of HLA class I

Recent data have shown that gut microbiota have a major impact on the clinical response to immune checkpoint inhibitors (ICIs). ICI therapy acts by unlocking tumor antigen (TA)-specific T cells and cancer clearance by TA-specific T cells requires expression of relevant TAs on cancer cells’ HLA class I molecules. Reduced HLA class I expression is a common mechanism used by cancer cells to evade the immune system, prompting out hypothesis that the presence of certain bacteria can enhance patien...

Targeting chemokine receptors to promote anti-tumor responses of neutrophils

Neutrophils represent a relevant component of the tumor microenvironment, and their presence in tumor tissue and high neutrophilia have been associated with poor prognosis in different oncological contexts, like high grade gliomas (HGGs). However, neutrophils are not a homogeneous population, and they can play a dichotomous role in cancer being both anti- and pro-tumoral. Indeed, tumor-derived cytokines induce the appearance in the blood of immature neutrophils with immunosuppressive activiti...