| Title | CD277 agonist enhances the immunogenicity of relapsed/refractory acute myeloid leukemia towards V delta 2(+) T cell cytotoxicity |
| Authors | Dong, Tianhui Wu, Ning Gao, Haitao Liang, Shuang Dong, Xinyu Zhao, Ting Jiang, Qian Liu, Jiangying |
| Affiliation | Peking Univ, Peoples Hosp, Natl Clin Res Ctr Hematol Dis, Inst Hematol,Beijing Key Lab Hematopoiet Stem Cel, 11 Xizhimen South St, Beijing 100044, Peoples R China Peking Univ, Acad Adv Interdisciplinary Studies, Peking Tsinghua Ctr Life Sci, Beijing, Peoples R China |
| Keywords | AML IMMUNOTHERAPY STIMULATION CONTRIBUTES ACTIVATION |
| Issue Date | Aug-2022 |
| Publisher | ANNALS OF HEMATOLOGY |
| Abstract | Relapse and refractoriness remain the major obstacles in clinical treatment of acute myeloid leukemia (AML). Efficacy of current therapeutic strategies for relapsed/refractory (R/R) AML is generally unsatisfying. V delta 2(+) T cells have become an attractive candidate for immunotherapy of various types of tumors. However, the results were not exciting in some pilot studies utilizing V delta 2 cell-based protocols to treat R/R AML. Functional receptors on V delta 2 cells and immunogenic ligands on leukemia cells are both critical to the anti-AML effect of V delta 2 cells, which have not been characterized in the context of R/R AML. CD277 can bind to phosphoantigens and promote the activation of V delta 2 cells. Anti-CD277 (clone 20.1) monoclonal antibody (20.1 mAb) has been identified as an agonist of CD277. Whether 20.1 mAb sensitizes R/R AML cells awaits investigation. Herein, we showed that the expressions of activating receptors on V delta 2 cells and CD277 on leukemia cells were deficient in patients with R/R AML. While agonists for NKG2D and TRAIL ligands did not increase the immunogenicity of R/R AML cells, 20.1 mAb significantly enhanced the cytotoxicity of V delta 2 cells on the drug-resistant human AML cell line and different types of primary AML cells from R/R patients. The sensitizing effect of 20.1 mAb was dependent on inducing degranulation of V delta 2 cells. These findings suggest a decisive role of CD277 in mediating the recognition of R/R AML cells by V delta 2(+) T cells. CD277 agonist combining adoptive transfer of V delta 2(+) T cells may improve the efficacy in the treatment of R/R AML. |
| URI | http://hdl.handle.net/20.500.11897/650103 |
| ISSN | 0939-5555 |
| DOI | 10.1007/s00277-022-04930-8 |
| Indexed | SCI(E) |
| Appears in Collections: | 人民医院 前沿交叉学科研究院 |
