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Identification of genomic signatures in bone marrow associated with clinical response of CD19 CAR T-cell therapy.
Shao, Lipei; Iyer, Avinash; Zhao, Yingdong; Somerville, Rob; Panch, Sandhya; Pelayo, Alejandra; Stroncek, David F; Jin, Ping.
Afiliación
  • Shao L; Center for Cellular Engineering, Department of Transfusion Medicine and Cellular Engineering, NIH Clinical Center, Bethesda, MD, USA.
  • Iyer A; Center for Cellular Engineering, Department of Transfusion Medicine and Cellular Engineering, NIH Clinical Center, Bethesda, MD, USA.
  • Zhao Y; Biometric Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Rockville, MD, USA.
  • Somerville R; Center for Cellular Engineering, Department of Transfusion Medicine and Cellular Engineering, NIH Clinical Center, Bethesda, MD, USA.
  • Panch S; Center for Cellular Engineering, Department of Transfusion Medicine and Cellular Engineering, NIH Clinical Center, Bethesda, MD, USA.
  • Pelayo A; Center for Cellular Engineering, Department of Transfusion Medicine and Cellular Engineering, NIH Clinical Center, Bethesda, MD, USA.
  • Stroncek DF; Center for Cellular Engineering, Department of Transfusion Medicine and Cellular Engineering, NIH Clinical Center, Bethesda, MD, USA.
  • Jin P; Center for Cellular Engineering, Department of Transfusion Medicine and Cellular Engineering, NIH Clinical Center, Bethesda, MD, USA. PJin@mail.cc.nih.gov.
Sci Rep ; 12(1): 2830, 2022 02 18.
Article en En | MEDLINE | ID: mdl-35181722
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.
Asunto(s)

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Células de la Médula Ósea / Leucemia Linfocítica Crónica de Células B / Inmunoterapia Adoptiva / Antígenos CD19 Tipo de estudio: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Idioma: En Revista: Sci Rep Año: 2022 Tipo del documento: Article

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Células de la Médula Ósea / Leucemia Linfocítica Crónica de Células B / Inmunoterapia Adoptiva / Antígenos CD19 Tipo de estudio: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Idioma: En Revista: Sci Rep Año: 2022 Tipo del documento: Article