Identification of genomic signatures in bone marrow associated with clinical response of CD19 CAR T-cell therapy.
Sci Rep
; 12(1): 2830, 2022 02 18.
Article
em En
| MEDLINE
| ID: mdl-35181722
ABSTRACT
CD19 CAR T-cell immunotherapy is a breakthrough treatment for B cell malignancies, but relapse and lack of response remain a challenge. The bone marrow microenvironment is a key factor in therapy resistance, however, little research has been reported concerning the relationship between transcriptomic profile of bone marrow prior to lymphodepleting preconditioning and clinical response following CD19 CAR T-cell therapy. Here, we applied comprehensive bioinformatic methods (PCA, GO, GSEA, GSVA, PAM-tools) to identify clinical CD19 CAR T-cell remission-related genomic signatures. In patients achieving a complete response (CR) transcriptomic profiles of bone marrow prior to lymphodepletion showed genes mainly involved in T cell activation. The bone marrow of CR patients also showed a higher activity in early T cell function, chemokine, and interleukin signaling pathways. However, non-responding patients showed higher activity in cell cycle checkpoint pathways. In addition, a 14-gene signature was identified as a remission-marker. Our study indicated the indexes of the bone marrow microenvironment have a close relationship with clinical remission. Enhancing T cell activation pathways (chemokine, interleukin, etc.) in the bone marrow before CAR T-cell infusion may create a pro-inflammatory environment which improves the efficacy of CAR T-cell therapy.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células da Medula Óssea
/
Leucemia Linfocítica Crônica de Células B
/
Imunoterapia Adotiva
/
Antígenos CD19
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos