https://scholars.lib.ntu.edu.tw/handle/123456789/641583
標題: | Immune profiling of patients with extranodal natural killer/T cell lymphoma treated with daratumumab | 作者: | Qing, Min Zhou, Tianyuan Perova, Tatiana Abraham, Yann Sweeney, Cheryl Krevvata, Maria Zhang, Xiaokang Qi, Ming Gao, Grace Kim, Tae Min MING YAO Cho, Seok-Goo Eom, Hyeon Seok Lim, Soon Thye Yeh, Su-Peng Kwong, Yok Lam Yoon, Dok Hyun Kim, Jin Seok Kim, Won Seog Zhou, Longen Attar, Ricardo Verona, Raluca I |
關鍵字: | Biomarkers; Daratumumab; Immune profiling; Natural killer/T cell lymphoma | 公開日期: | 18-一月-2024 | 來源出版物: | Annals of hematology | 摘要: | Natural killer/T cell lymphoma (NKTCL) is a highly aggressive, heterogeneous non-Hodgkin lymphoma resulting from malignant proliferation of cytotoxic natural killer (NK) or T cells. Previous studies demonstrated variable expression of CD38 on NKTCL tumors. Daratumumab, a human IgGκ monoclonal antibody targeting CD38 with a direct on-tumor and immunomodulatory mechanism of action, was hypothesized to be a novel therapeutic option for patients with relapsed or refractory (R/R) NKTCL. In the phase 2 NKT2001 study (ClinicalTrials.gov Identifier: NCT02927925) assessing the safety and efficacy of daratumumab, a suboptimal overall response rate was seen in R/R NKTCL patients. One patient, whose tumors did not express CD38, responded to treatment, suggesting that the immunomodulatory activities of daratumumab may be sufficient to confer clinical benefit. To understand the suboptimal response rate and short duration of response, we investigated the immune profile of NKTCL patients from NKT2001 in the context of daratumumab anti-tumor activity. Tumor tissue and whole blood were, respectively, analyzed for CD38 expression and patient immune landscapes, which were assessed via cytometry by time-of-flight (CyTOF), multiparameter flow cytometry (MPFC), clonal sequencing, and plasma Epstein-Barr virus (EBV)-DNA level measurements. Changes observed in the immune profiles of NKTCL patients from NKT2001, including differences in B and T cell populations between responders and nonresponders, suggest that modulation of the immune environment is crucial for daratumumab anti-tumor activities in NKTCL. In conclusion, these findings highlight that the clinical benefit of daratumumab in NKTCL may be enriched by B/T cell-related biomarkers. |
URI: | https://www.scopus.com/record/display.uri?eid=2-s2.0-85182447526&doi=10.1007%2fs00277-023-05603-w&origin=inward&txGid=338b2b1b073be394dcc9d6b9a891a849 https://scholars.lib.ntu.edu.tw/handle/123456789/641583 |
ISSN: | 09395555 | DOI: | 10.1007/s00277-023-05603-w |
顯示於: | 醫學系 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。