Single cell analysis of the CD8+ T-cell compartment in multiple myeloma reveals disease specific changes are chiefly restricted to a CD69- subset suggesting potent cytotoxic effectors exist within the tumor bed.

Favaloro, J; Bryant, CE; Abadir, E; Gardiner, S; Yang, S; King, T; Nassif, N; Sedger, LM; Boyle, R; Joshua, DE; Ho, PJ

Single cell analysis of the CD8+ T-cell compartment in multiple myeloma reveals disease specific changes are chiefly restricted to a CD69- subset suggesting potent cytotoxic effectors exist within the tumor bed.

Favaloro, J Bryant, CE Abadir, E Gardiner, S Yang, S King, T Nassif, N

Sedger, LM Boyle, R Joshua, DE Ho, PJ

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Publisher:: Ferrata Storti Foundation (Haematologica)
Publication Type:: Journal Article
Citation:: Haematologica, 2023
Issue Date:: 2023-10-05

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Field	Value	Language
dc.contributor.author	Favaloro, J
dc.contributor.author	Bryant, CE
dc.contributor.author	Abadir, E
dc.contributor.author	Gardiner, S
dc.contributor.author	Yang, S
dc.contributor.author	King, T
dc.contributor.author	Nassif, N https://orcid.org/0000-0003-2675-8322
dc.contributor.author	Sedger, LM
dc.contributor.author	Boyle, R
dc.contributor.author	Joshua, DE
dc.contributor.author	Ho, PJ
dc.date.accessioned	2023-12-05T06:54:02Z
dc.date.available	2023-12-05T06:54:02Z
dc.date.issued	2023-10-05
dc.identifier.citation	Haematologica, 2023
dc.identifier.issn	0390-6078
dc.identifier.issn	1592-8721
dc.identifier.uri	http://hdl.handle.net/10453/173720
dc.description.abstract	Multiple Myeloma (MM) is an incurable disease of the bone marrow (BM) characterized by the uncontrolled proliferation of neoplastic plasma cells. While CD8+ T-cells have an established role in disease control, few studies have focused on these cells within the MM tumor microenvironment (TME). We analyzed CD8+ T-cells in the BM and peripheral blood (PB) of untreated patients with MM and non-myeloma controls using flow cytometry, mass cytometry and single-cell RNA sequencing, using several novel bioinformatics workflows. Inter-tissue differences were most evident in the differential expression of granzymes B and K, which were strongly associated with two distinct subsets of CD8+ T-cells delineated by the expression of CD69, accounting for roughly 50% of BM-CD8+ T-cells of all assessed cohorts. While few differences were observable between health and disease in the BM-restricted CD8CD69+ T-cell subset, the CD8+CD69- T-cell subset in the BM of untreated MM patients demonstrated increased representation of highly differentiated effector cells and evident compositional parallels between the PB, absent in age-matched controls, where a marked reduction of effector cells was observed. We demonstrate the transcriptional signature of BM-CD8+ T-cells from patients with MM more closely resembles TCR-activated CD8+ T-cells from age-matched controls than their resting counterparts.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	Ferrata Storti Foundation (Haematologica)
dc.relation.ispartof	Haematologica
dc.relation.isbasedon	10.3324/haematol.2023.283062
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	1102 Cardiorespiratory Medicine and Haematology
dc.subject.classification	Immunology
dc.subject.classification	3201 Cardiovascular medicine and haematology
dc.title	Single cell analysis of the CD8+ T-cell compartment in multiple myeloma reveals disease specific changes are chiefly restricted to a CD69- subset suggesting potent cytotoxic effectors exist within the tumor bed.
dc.type	Journal Article
utslib.location.activity	Italy
utslib.for	1102 Cardiorespiratory Medicine and Haematology
pubs.organisational-group	/University of Technology Sydney
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/Centre for Health Technologies (CHT)
utslib.copyright.status	closed_access	*
dc.date.updated	2023-12-05T06:54:01Z
pubs.publication-status	Published online

Abstract:

Multiple Myeloma (MM) is an incurable disease of the bone marrow (BM) characterized by the uncontrolled proliferation of neoplastic plasma cells. While CD8+ T-cells have an established role in disease control, few studies have focused on these cells within the MM tumor microenvironment (TME). We analyzed CD8+ T-cells in the BM and peripheral blood (PB) of untreated patients with MM and non-myeloma controls using flow cytometry, mass cytometry and single-cell RNA sequencing, using several novel bioinformatics workflows. Inter-tissue differences were most evident in the differential expression of granzymes B and K, which were strongly associated with two distinct subsets of CD8+ T-cells delineated by the expression of CD69, accounting for roughly 50% of BM-CD8+ T-cells of all assessed cohorts. While few differences were observable between health and disease in the BM-restricted CD8CD69+ T-cell subset, the CD8+CD69- T-cell subset in the BM of untreated MM patients demonstrated increased representation of highly differentiated effector cells and evident compositional parallels between the PB, absent in age-matched controls, where a marked reduction of effector cells was observed. We demonstrate the transcriptional signature of BM-CD8+ T-cells from patients with MM more closely resembles TCR-activated CD8+ T-cells from age-matched controls than their resting counterparts.

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http://hdl.handle.net/10453/173720