Inverse relationship between oligoclonal expanded CD69- TTE and CD69+ TTE cells in bone marrow of multiple myeloma patients.

Vuckovic, S; Bryant, CE; Lau, KHA; Yang, S; Favaloro, J; McGuire, HM; Clark, G; de St Groth, BF; Marsh-Wakefield, F; Nassif, N; Abadir, E; Vanguru, V; McCulloch, D; Brown, C; Larsen, S; Dunkley, S; Khoo, L; Gibson, J; Boyle, R; Joshua, D; Ho, PJ

Inverse relationship between oligoclonal expanded CD69- TTE and CD69+ TTE cells in bone marrow of multiple myeloma patients.

Vuckovic, S Bryant, CE Lau, KHA Yang, S Favaloro, J McGuire, HM Clark, G de St Groth, BF Marsh-Wakefield, F Nassif, N

Abadir, E Vanguru, V McCulloch, D Brown, C Larsen, S Dunkley, S Khoo, L Gibson, J Boyle, R Joshua, D Ho, PJ

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Publisher:: American Society of Hematology
Publication Type:: Journal Article
Citation:: Blood advances, 2020, 4, (19), pp. 4593-4604
Issue Date:: 2020-10

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Field	Value	Language
dc.contributor.author	Vuckovic, S
dc.contributor.author	Bryant, CE
dc.contributor.author	Lau, KHA
dc.contributor.author	Yang, S
dc.contributor.author	Favaloro, J
dc.contributor.author	McGuire, HM
dc.contributor.author	Clark, G
dc.contributor.author	de St Groth, BF
dc.contributor.author	Marsh-Wakefield, F
dc.contributor.author	Nassif, N https://orcid.org/0000-0003-2675-8322
dc.contributor.author	Abadir, E
dc.contributor.author	Vanguru, V
dc.contributor.author	McCulloch, D
dc.contributor.author	Brown, C
dc.contributor.author	Larsen, S
dc.contributor.author	Dunkley, S
dc.contributor.author	Khoo, L
dc.contributor.author	Gibson, J
dc.contributor.author	Boyle, R
dc.contributor.author	Joshua, D
dc.contributor.author	Ho, PJ
dc.date.accessioned	2020-12-17T00:17:52Z
dc.date.available	2020-08-24
dc.date.available	2020-12-17T00:17:52Z
dc.date.issued	2020-10
dc.identifier.citation	Blood advances, 2020, 4, (19), pp. 4593-4604
dc.identifier.issn	2473-9529
dc.identifier.issn	2473-9537
dc.identifier.uri	http://hdl.handle.net/10453/144783
dc.description.abstract	CD8+CD57+ terminal effector T (TTE) cells are a component of marrow-infiltrating lymphocytes and may contribute to the altered immune responses in multiple myeloma (MM) patients. We analyzed TTE cells in the bone marrow (BM) and peripheral blood (PB) of age-matched controls and patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering MM (SMM), and newly diagnosed (ND) MM using flow cytometry, mass cytometry, and FlowSOM clustering. TTE cells are heterogeneous in all subjects, with BM containing both CD69- and CD69+ subsets, while only CD69- cells are found in PB. Within the BM-TTE compartment, CD69- and CD69+ cells are found in comparable proportions in controls, while CD69- cells are dominant in MGUS and SMM and predominantly either CD69- or CD69+ cells in NDMM. A positive relationship between CD69+TTE and CD69-TTE cells is observed in the BM of controls, lost in MGUS, and converted to an inverse relationship in NDMM. CD69-TTE cells include multiple oligoclonal expansions of T-cell receptor/Vβ families shared between BM and PB of NDMM. Oligoclonal expanded CD69-TTE cells from the PB include myeloma-reactive cells capable of killing autologous CD38hi plasma cells in vitro, involving degranulation and high expression of perforin and granzyme. In contrast to CD69-TTE cells, oligoclonal expansions are not evident within CD69+TTE cells, which possess low perforin and granzyme expression and high inhibitory checkpoint expression and resemble T resident memory cells. Both CD69-TTE and CD69+TTE cells from the BM of NDMM produce large amounts of the inflammatory cytokines interferon-γ and tumor necrosis factor α. The balance between CD69- and CD69+ cells within the BM-TTE compartment may regulate immune responses in NDMM and contribute to the clinical heterogeneity of the disease.
dc.format	Print
dc.language	eng
dc.publisher	American Society of Hematology
dc.relation.ispartof	Blood advances
dc.relation.isbasedon	10.1182/bloodadvances.2020002237
dc.rights	info:eu-repo/semantics/openAccess
dc.title	Inverse relationship between oligoclonal expanded CD69- TTE and CD69+ TTE cells in bone marrow of multiple myeloma patients.
dc.type	Journal Article
utslib.citation.volume	4
utslib.location.activity	United States
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney
utslib.copyright.status	open_access	*
pubs.consider-herdc	false
dc.date.updated	2020-12-17T00:17:47Z
pubs.issue	19
pubs.publication-status	Published
pubs.volume	4
utslib.citation.issue	19

Abstract:

CD8+CD57+ terminal effector T (TTE) cells are a component of marrow-infiltrating lymphocytes and may contribute to the altered immune responses in multiple myeloma (MM) patients. We analyzed TTE cells in the bone marrow (BM) and peripheral blood (PB) of age-matched controls and patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering MM (SMM), and newly diagnosed (ND) MM using flow cytometry, mass cytometry, and FlowSOM clustering. TTE cells are heterogeneous in all subjects, with BM containing both CD69- and CD69+ subsets, while only CD69- cells are found in PB. Within the BM-TTE compartment, CD69- and CD69+ cells are found in comparable proportions in controls, while CD69- cells are dominant in MGUS and SMM and predominantly either CD69- or CD69+ cells in NDMM. A positive relationship between CD69+TTE and CD69-TTE cells is observed in the BM of controls, lost in MGUS, and converted to an inverse relationship in NDMM. CD69-TTE cells include multiple oligoclonal expansions of T-cell receptor/Vβ families shared between BM and PB of NDMM. Oligoclonal expanded CD69-TTE cells from the PB include myeloma-reactive cells capable of killing autologous CD38hi plasma cells in vitro, involving degranulation and high expression of perforin and granzyme. In contrast to CD69-TTE cells, oligoclonal expansions are not evident within CD69+TTE cells, which possess low perforin and granzyme expression and high inhibitory checkpoint expression and resemble T resident memory cells. Both CD69-TTE and CD69+TTE cells from the BM of NDMM produce large amounts of the inflammatory cytokines interferon-γ and tumor necrosis factor α. The balance between CD69- and CD69+ cells within the BM-TTE compartment may regulate immune responses in NDMM and contribute to the clinical heterogeneity of the disease.

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http://hdl.handle.net/10453/144783