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T cell phenotype and clonality changes in myeloma patients with short overall survival
Alenka Djarmila Behsen, Esten Nymoen Vandsemb, Tobias Schmidt Slørdahl, Karen Dybkær, Maja Zimmer Jakobsen, Muhammad Kashif, Johan Lund, Vincent Luong, Astrid Marta Olsnes, Anders Waage, Anne Marit Sponaas, Kristine Misund
Alenka Djarmila Behsen, Esten Nymoen Vandsemb, Tobias Schmidt Slørdahl, Karen Dybkær, Maja Zimmer Jakobsen, Muhammad Kashif, Johan Lund, Vincent Luong, Astrid Marta Olsnes, Anders Waage, Anne Marit Sponaas, Kristine Misund
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Research Article Hematology Immunology Oncology

T cell phenotype and clonality changes in myeloma patients with short overall survival

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Abstract

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

Alenka Djarmila Behsen, Esten Nymoen Vandsemb, Tobias Schmidt Slørdahl, Karen Dybkær, Maja Zimmer Jakobsen, Muhammad Kashif, Johan Lund, Vincent Luong, Astrid Marta Olsnes, Anders Waage, Anne Marit Sponaas, Kristine Misund

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Figure 4

Mass cytometry analysis of naive, memory, and effector CD8+ T cell populations.

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Mass cytometry analysis of naive, memory, and effector CD8+ T cell popul...
Percentage of (A) TCM (CD45RA–CD45RO+CCR7+), TEM (CD45RA–CD45RO+CCR7–), TEMRA (CD45RA+CD45RO–CCR7–), and naive CD8+ T cells (CD45RA+CD45RO–CCR7+) within the CD8+ T cell population; (B) CD95– and CD95+ naive CD8+ T cells within the naive CD8+ T cell population; and (C) MMI of KLRG-1, Eomes, T-bet, and granzyme B within the naive CD8+ T cell population, in the BM of patients with myeloma and age-matched HCs (n = 6). Paired diagnosis and last relapse samples from n = 11 long-OS patients and n = 10 short-OS patients were included. Mean ± SEM shown. Statistical significance was determined by repeated measures 2-way ANOVA and Šidák’s multiple comparisons test on long-OS and short-OS patient samples. Data from HCs are also shown. P values are indicated where P < 0.05.

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