T cell phenotype and clonality changes in myeloma patients with short overall survival
Overall survival (OS) in multiple myeloma (MM) varies between a couple of months to more than 20 years, influenced by tumor characteristics, the tumor microenvironment (TME), and patient factors such as age and frailty. We analyzed sequential BM samples from 45 MM patients with OS less than 3 years versus more than 8 years using mass cytometry and bulk TCRβ sequencing. Patients with long OS demonstrated stability in the TME and T cell environments, while those with short OS had significant changes at relapse, including fewer T cells, increased Tregs, and more activated and exhausted CD8+ T cells. Notably, higher programmed cell death 1 expression in CD8+ T cells at diagnosis correlated with short OS. Additionally, short-OS patients exhibited a more monoclonal T cell environment at relapse, with abundance of hyperexpanded clones. These findings reveal distinct immune cell differences between patients with short and long OS.
Authors
- Karen Dybkær (ORCID: https://orcid.org/0000-0003-2488-435X)
- Esten N. Vandsemb (ORCID: https://orcid.org/0000-0002-5883-437X)
- Alenka Djarmila Behsen
- Astrid Marta Olsnes
- Vincent Luong (ORCID: https://orcid.org/0000-0001-9825-6706)
- Anders Waage (ORCID: https://orcid.org/0000-0001-9072-1220)
- Kristine Misund (ORCID: https://orcid.org/0000-0002-8742-7028)
- Tobias S. Slørdahl (ORCID: https://orcid.org/0000-0001-7488-4863)
- Anne‐Marit Sponaas (ORCID: https://orcid.org/0000-0002-0860-8446)
- Muhammad Kashif (ORCID: https://orcid.org/0000-0002-7545-8548)
- Maja Zimmer Jakobsen
- Johan Lund (ORCID: https://orcid.org/0000-0002-5364-3670)
Institutions
- Karolinska University Hospital (SE)
- Norwegian University of Science and Technology (NO)
- Aalborg University Hospital (DK)
- Haukeland University Hospital (NO)
- Karolinska Institutet (SE)
- St Olav's University Hospital (NO)
- University of Bergen (NO)
- Aalborg University (DK)
Publication Details
- Journal
- JCI Insight
- Published
- 2025-04-22
- DOI
- https://doi.org/10.1172/jci.insight.181096
- Primary Topic
- Multiple Myeloma Research and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Amgen
- Bristol-Myers Squibb
- Pfizer
- GlaxoSmithKline
- Celgene
- Norges Teknisk-Naturvitenskapelige Universitet
- Helse Midt-Norge
- Universitetet i Bergen
- St. Olavs Hospital Universitetssykehuset i Trondheim
- Fakultet for medisin og helsevitenskap, Norges Teknisk-Naturvitenskapelige Universitet
- Faculty of Medicine and Health, University of Sydney
- Cilag