PMID- 26185130
OWN - NLM
STAT- MEDLINE
DCOM- 20151215
LR  - 20210202
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 126
IP  - 12
DP  - 2015 Sep 17
TI  - Dendritic cells accumulate in the bone marrow of myeloma patients where they 
      protect tumor plasma cells from CD8+ T-cell killing.
PG  - 1443-51
LID - 10.1182/blood-2015-01-623975 [doi]
AB  - Many researchers have speculated that the clinical progression from monoclonal 
      gammopathy of undetermined significance (MGUS) to multiple myeloma (MM) is driven 
      by defects in dendritic cell (DC) function. However, evidence supporting this 
      assumption is controversial, and no mechanism for the putative DC dysfunction has 
      been demonstrated thus far. We studied DC subsets from the bone marrow of MM 
      patients compared with those of MGUS patients and control subjects. We found that 
      myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) accumulate in the bone marrow 
      during the MGUS-to-MM progression. After engulfment of apoptotic tumor plasma 
      cells via CD91, bone marrow mDCs and pDCs mature and are able to activate 
      tumor-specific CD8(+) T cells. However, by interacting directly with CD28 on live 
      (nonapoptotic) tumor plasma cells, bone marrow mDCs downregulate the expression 
      of proteasome subunits in these cells, thus enabling their evasion from human 
      leukocyte antigen (HLA) class I-restricted CD8(+) T-cell killing. These results 
      suggest that DCs play a dual, but opposing, role in MM: for one, DCs activate 
      CD8(+) T cells against tumor plasma cells and, for the other, DCs protect tumor 
      plasma cells from CD8(+) T-cell killing. This information should be taken into 
      account in designing immunotherapy approaches to enhance immune surveillance in 
      MGUS and to break down immune tolerance in MM.
CI  - (c) 2015 by The American Society of Hematology.
FAU - Leone, Patrizia
AU  - Leone P
AD  - Department of Internal Medicine and Clinical Oncology, University of Bari Medical 
      School, Bari, Italy;
FAU - Berardi, Simona
AU  - Berardi S
AD  - Department of Internal Medicine and Clinical Oncology, University of Bari Medical 
      School, Bari, Italy;
FAU - Frassanito, Maria Antonia
AU  - Frassanito MA
AD  - Department of Internal Medicine and Clinical Oncology, University of Bari Medical 
      School, Bari, Italy;
FAU - Ria, Roberto
AU  - Ria R
AD  - Department of Internal Medicine and Clinical Oncology, University of Bari Medical 
      School, Bari, Italy;
FAU - De Re, Valli
AU  - De Re V
AD  - Bio-Proteomics Facility, Department of Translational Research, Centro di 
      Riferimento Oncologico, National Cancer Institute, Aviano, Italy; and.
FAU - Cicco, Sebastiano
AU  - Cicco S
AD  - Department of Internal Medicine and Clinical Oncology, University of Bari Medical 
      School, Bari, Italy;
FAU - Battaglia, Stefano
AU  - Battaglia S
AD  - Department of Internal Medicine and Clinical Oncology, University of Bari Medical 
      School, Bari, Italy;
FAU - Ditonno, Paolo
AU  - Ditonno P
AD  - Hematology Unit, Di Venere Hospital, Bari, Italy.
FAU - Dammacco, Franco
AU  - Dammacco F
AD  - Department of Internal Medicine and Clinical Oncology, University of Bari Medical 
      School, Bari, Italy;
FAU - Vacca, Angelo
AU  - Vacca A
AD  - Department of Internal Medicine and Clinical Oncology, University of Bari Medical 
      School, Bari, Italy;
FAU - Racanelli, Vito
AU  - Racanelli V
AD  - Department of Internal Medicine and Clinical Oncology, University of Bari Medical 
      School, Bari, Italy;
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150716
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
SB  - IM
CIN - Blood. 2015 Sep 17;126(12):1401-3. PMID: 26384282
MH  - Bone Marrow/immunology/*pathology
MH  - CD8-Positive T-Lymphocytes/immunology/*pathology
MH  - Cell Death
MH  - Cells, Cultured
MH  - Dendritic Cells/*immunology/pathology
MH  - Humans
MH  - Multiple Myeloma/immunology/*pathology
MH  - Plasma Cells/immunology/*pathology
MH  - Plasmacytoma/immunology/*pathology
MH  - Tumor Cells, Cultured
PMC - PMC4592278
EDAT- 2015/07/18 06:00
MHDA- 2015/12/17 06:00
PMCR- 2015/09/17
CRDT- 2015/07/18 06:00
PHST- 2015/01/26 00:00 [received]
PHST- 2015/07/08 00:00 [accepted]
PHST- 2015/07/18 06:00 [entrez]
PHST- 2015/07/18 06:00 [pubmed]
PHST- 2015/12/17 06:00 [medline]
PHST- 2015/09/17 00:00 [pmc-release]
AID - S0006-4971(20)30910-1 [pii]
AID - 2015/623975 [pii]
AID - 10.1182/blood-2015-01-623975 [doi]
PST - ppublish
SO  - Blood. 2015 Sep 17;126(12):1443-51. doi: 10.1182/blood-2015-01-623975. Epub 2015 
      Jul 16.