Ricerc@Sapienza

Purpose: This study was aimed at evaluating the feasibility, safety, immunological and clinical responses in patients with Follicular lymphoma (FL) treated with monocyte-derived dendritic cells generated in the presence of interferon-alpha and GM-CSF (IFN-DC) in combination with low doses of Rituximab (R). Experimental Design: Firstly, we analyzed in vitro and in vivo the immunological properties of IFN-DC against FL.

Tyrosine kinase inhibitors (TKIs) target angiogenesis by affecting,
for example, the VEGF receptors in tumors and have
improved outcomes for patients with metastatic renal cell carcinoma
(mRCC). Immune checkpoint inhibitors (ICIs) have
also been proposed for treatment of mRCC with encouraging
results. A better understanding of the activity of immune cells in
mRCC, the immunomodulatory effects of TKIs, and the characteristics
defining patients most likely to benefit from various

Tumor cells release extracellular microvesicles (MVs) in the microenvironment to deliver biological signals to neighbouring cells as well as to cells in distant tissues.
Tumor-derived MVs appear to play contradictory role promoting both immunosuppression and tumor growth and both evoking tumor specific immune response. Recent evidences indicate that tumor-derived MVs can positively impact Dendritic Cells (DCs) immunogenicity by reprogramming DC antigen processing machinery and intracellular signaling pathways, thus promoting anti-tumor response.

Dendritic cells (DCs) are the only antigen-presenting cells able to prime naïve T cells and
cross-prime antigen-specific CD8+ T cells. Their functionality is a requirement for the
induction and maintenance of long-lasting cancer immunity. Albeit intensively investigated,
the in vivo mechanisms underlying efficient antigen cross-processing and presentation
are not fully understood. Several pieces of evidence indicate that antigen transfer to DCs
mediated by microvesicles (MVs) enhances antigen immunogenicity. This mechanism

HHV-6A and HHV-6B are ubiquitous human betaherpesviruses sharing more than 80% homology. HHV-6B is the most common cause of encephalitis in transplant patients and its primary infection may cause the exanthema subitum and febrile seizures in infants. HHV-6A and HHV-6B are able to infect several immune cell types such as T cells, monocytes and dendritic cells (DCs). In this study we found that HHV-6 B derived from patients affected by exanthema subitum impaired monocyte differentiation into DCs, as the infected cells acquired less CD1a DC marker and retained more CD14 monocyte marker.

EBV has been reported to impair monocyte in vitro differentiation into dendritic cells (DCs) and reduce cell survival. In this study, we added another layer of knowledge to this topic and showed that these effects correlated with macroautophagy/autophagy, ROS and mitochondrial biogenesis reduction. Of note, autophagy and ROS, although strongly interconnected, have been separately reported to be induced by CSF2/GM-CSF (colony stimulating factor 2) and required for CSF2-IL4-driven monocyte in vitro differentiation into DCs.