Treatment Induced Cytotoxic T-Cell Modulation in Multiple Myeloma Patients.
ASCT-autologous stem cell transplantation
cytotoxic response
immunophenotyping
lenalidomide
multiple myeloma
treatment
Journal
Frontiers in oncology
ISSN: 2234-943X
Titre abrégé: Front Oncol
Pays: Switzerland
ID NLM: 101568867
Informations de publication
Date de publication:
2021
2021
Historique:
received:
18
03
2021
accepted:
10
05
2021
entrez:
2
7
2021
pubmed:
3
7
2021
medline:
3
7
2021
Statut:
epublish
Résumé
The biology of plasma cell dyscrasias (PCD) involves both genetic and immune-related factors. Since genetic lesions are necessary but not sufficient for Multiple Myeloma (MM) evolution, several authors hypothesized that immune dysfunction involving both B and T cell counterparts plays a key role in the pathogenesis of the disease. The aim of this study is to evaluate the impact of cornerstone treatments for Multiple Myeloma into immune system shaping. A large series of 976 bone marrow samples from 735 patients affected by PCD was studied by flow analysis to identify discrete immune subsets. Treated MM samples displayed a reduction of CD4+ cells (p<0.0001) and an increase of CD8+ (p<0.0001), CD8+/DR+ (p<0.0001) and CD3+/CD57+ (p<0.0001) cells. Although these findings were to some extent demonstrated also following bortezomib treatment, a more pronounced cytotoxic polarization was shown after exposure to autologous stem cell transplantation (ASCT) and Lenalidomide (Len) treatment. As a matter of fact, samples of patients who received ASCT (n=110) and Len (n=118) were characterized, towards untreated patients (n=138 and n=130, respectively), by higher levels of CD8+ (p<0.0001 and p<0.0001, respectively), CD8+/DR+ (p=0.0252 and p=0.0001, respectively) and CD3+/CD57+ cells (p<0.0001 and p=0.0006, respectively) and lower levels of CD4+ lymphocytes (p<0.0001 and p=0.0005, respectively). We demonstrated that active MM patients are characterized by a relevant T cell modulation and that most of these changes are therapy-related. Current Myeloma treatments, notably ASCT and Len treatments, polarize immune system towards a dominant cytotoxic response, likely contributing to the anti-Myeloma effect of these regimens.
Identifiants
pubmed: 34211851
doi: 10.3389/fonc.2021.682658
pmc: PMC8239308
doi:
Types de publication
Journal Article
Langues
eng
Pagination
682658Informations de copyright
Copyright © 2021 Barilà, Pavan, Vedovato, Berno, Lo Schirico, Arangio Febbo, Teramo, Calabretto, Vicenzetto, Gasparini, Fregnani, Manni, Trimarco, Carraro, Facco, Piazza, Semenzato and Zambello.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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