Dendritic cells accumulate in the bone marrow of myeloma patients where they protect tumor plasma cells from CD8+ T-cell killing

Patrizia Leone, Simona Berardi, Maria Antonia Frassanito, Roberto Ria, Valli De Re, Sebastiano Cicco, Stefano Battaglia, Paolo Ditonno, Franco Dammacco, Angelo Vacca, Vito Racanelli

Research output: Contribution to journalArticle

Abstract

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 engulfmentof apoptotic tumor plasma cells viaCD91, bonemarrowm DCs and pDCs mature and are able to activate tumor-specific CD8+ T cells. However, by interacting directly with CD28onlive (nonapoptotic) tumor plasma cells, bonemarrowmDCsdownregulate 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 activateCD8+ T cells against tumor plasmacells and, for the other, DCs protect tumor plasmacells fromCD8+T-cell killing.This informationshouldbetakenintoaccount indesigningimmunotherapyapproachestoenhance immune surveillance in MGUS and to break down immune tolerance in MM.

Original languageEnglish
Pages (from-to)1443-1451
Number of pages9
JournalBlood
Volume126
Issue number12
DOIs
Publication statusPublished - Sep 17 2015

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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    Leone, P., Berardi, S., Frassanito, M. A., Ria, R., De Re, V., Cicco, S., Battaglia, S., Ditonno, P., Dammacco, F., Vacca, A., & Racanelli, V. (2015). Dendritic cells accumulate in the bone marrow of myeloma patients where they protect tumor plasma cells from CD8+ T-cell killing. Blood, 126(12), 1443-1451. https://doi.org/10.1182/blood-2015-01-623975