| Autor: |
Jiachen Wang, Kefeng Shen, Wei Mu, Weigang Li, Meilan Zhang, Wei Zhang, Zhe Li, Tong Ge, Zhoujie Zhu, Shangkun Zhang, Caixia Chen, Shugang Xing, Li Zhu, Liting Chen, Na Wang, Liang Huang, Dengju Li, Min Xiao, Jianfeng Zhou |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Frontiers in Immunology, Vol 13 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
1664-3224 |
| DOI: |
10.3389/fimmu.2022.873789 |
| Popis: |
Despite impressive progress, a significant portion of patients still experience primary or secondary resistance to chimeric antigen receptor (CAR) T-cell immunotherapy for relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL). The mechanism of primary resistance involves T-cell extrinsic and intrinsic dysfunction. In the present study, a total of 135 patients of DLBCL treated with murine CD19/CD22 cocktail CAR T-therapy were assessed retrospectively. Based on four criteria (maximal expansion of the transgene/CAR-positive T-cell levels post-infusion [Cmax], initial persistence of the transgene by the CAR transgene level at +3 months [Tlast], CD19+ B-cell levels [B-cell recovery], and the initial response to CAR T-cell therapy), 48 patients were included in the research and divided into two groups (a T-normal group [n=22] and a T-defect [n=26] group). According to univariate and multivariate regression analyses, higher lactate dehydrogenase (LDH) levels before leukapheresis (hazard ratio (HR) = 1.922; p = 0.045) and lower cytokine release syndrome (CRS) grade after CAR T-cell infusion (HR = 0.150; p = 0.026) were independent risk factors of T-cell dysfunction. Moreover, using whole-exon sequencing, we found that germline variants in 47 genes were significantly enriched in the T-defect group compared to the T-normal group (96% vs. 41%; p |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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