PMID- 28993771
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 1664-3224 (Print)
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 8
DP  - 2017
TI  - Tumor-Derived Microvesicles Modulate Antigen Cross-Processing via Reactive Oxygen 
      Species-Mediated Alkalinization of Phagosomal Compartment in Dendritic Cells.
PG  - 1179
LID - 10.3389/fimmu.2017.01179 [doi]
LID - 1179
AB  - Dendritic cells (DCs) are the only antigen-presenting cells able to prime naive 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 is also 
      relevant for cross-presentation of those tumor-associated glycoproteins such as 
      MUC1 that are blocked in HLA class II compartment when internalized by DCs as 
      soluble molecules. Here, we present pieces of evidence that the internalization 
      of tumor-derived MVs modulates antigen-processing machinery of DCs. Employing MVs 
      derived from ovarian cancer ascites fluid and established tumor cell lines, we 
      show that MV uptake modifies DC phagosomal microenvironment, triggering reactive 
      oxygen species (ROS) accumulation and early alkalinization. Indeed, tumor MVs 
      carry radical species and the MV uptake by DCs counteracts the chemically 
      mediated acidification of the phagosomal compartment. Further pieces of evidence 
      suggest that efficacious antigen cross-priming of the MUC1 antigen carried by the 
      tumor MVs results from the early signaling induced by MV internalization and the 
      function of the antigen-processing machinery of DCs. These results strongly 
      support the hypothesis that tumor-derived MVs impact antigen immunogenicity by 
      tuning the antigen-processing machinery of DCs, besides being carrier of tumor 
      antigens. Furthermore, these findings have important implications for the 
      exploitation of MVs as antigenic cell-free immunogen for DC-based therapeutic 
      strategies.
FAU - Battisti, Federico
AU  - Battisti F
AD  - Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
FAU - Napoletano, Chiara
AU  - Napoletano C
AD  - Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
FAU - Rahimi Koshkaki, Hassan
AU  - Rahimi Koshkaki H
AD  - Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
FAU - Belleudi, Francesca
AU  - Belleudi F
AD  - Department of Molecular and Clinical Medicine, Instituto Pasteur 
      Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, Italy.
FAU - Zizzari, Ilaria Grazia
AU  - Zizzari IG
AD  - Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
FAU - Ruscito, Ilary
AU  - Ruscito I
AD  - Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
AD  - Department of Gynaecology, Obstetrics and Urology, Sapienza University of Rome, 
      Rome, Italy.
FAU - Palchetti, Sara
AU  - Palchetti S
AD  - Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
FAU - Bellati, Filippo
AU  - Bellati F
AD  - Department of Medical and Surgical Sciences and Translational Medicine, Sapienza 
      University of Rome, Rome, Italy.
AD  - Azienda Ospedaliera Sant'Andrea, Rome, Italy.
FAU - Benedetti Panici, Pierluigi
AU  - Benedetti Panici P
AD  - Department of Gynaecology, Obstetrics and Urology, Sapienza University of Rome, 
      Rome, Italy.
FAU - Torrisi, Maria Rosaria
AU  - Torrisi MR
AD  - Department of Molecular and Clinical Medicine, Instituto Pasteur 
      Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, Italy.
AD  - Azienda Ospedaliera Sant'Andrea, Rome, Italy.
FAU - Caracciolo, Giulio
AU  - Caracciolo G
AD  - Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
FAU - Altieri, Fabio
AU  - Altieri F
AD  - Department of Biochemical Sciences "A. Rossi Fanelli", Sapienza University of 
      Rome, Rome, Italy.
FAU - Nuti, Marianna
AU  - Nuti M
AD  - Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
FAU - Rughetti, Aurelia
AU  - Rughetti A
AD  - Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
LA  - eng
PT  - Journal Article
DEP - 20170925
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
PMC - PMC5622295
OTO - NOTNLM
OT  - antigen-processing
OT  - cancer vaccines
OT  - dendritic cells
OT  - immune response to cancer
OT  - microvesicles
OT  - phagosome
OT  - radical oxigen species
OT  - tumor antigens
EDAT- 2017/10/11 06:00
MHDA- 2017/10/11 06:01
PMCR- 2017/01/01
CRDT- 2017/10/11 06:00
PHST- 2017/05/02 00:00 [received]
PHST- 2017/09/06 00:00 [accepted]
PHST- 2017/10/11 06:00 [entrez]
PHST- 2017/10/11 06:00 [pubmed]
PHST- 2017/10/11 06:01 [medline]
PHST- 2017/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2017.01179 [doi]
PST - epublish
SO  - Front Immunol. 2017 Sep 25;8:1179. doi: 10.3389/fimmu.2017.01179. eCollection 
      2017.