Reversal of T-cell tolerance in myelodysplastic syndrome through lenalidomide immune modulation.
Reversal of T-cell tolerance in myelodysplastic syndrome through lenalidomide immune modulation.
复制标题
通过来那度胺免疫调节逆转骨髓增生异常综合征中的 T 细胞耐受性。
DOI：
10.1038/leu.2011.359
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发表时间：
2012
期刊：
影响因子：
11.4
通讯作者：
Epling-Burnette,PK
中科院分区：
文献类型：
--
作者：
McDaniel,JM;Zou,JX;Fulp,W;Chen,D-T;List,AF;Epling-Burnette,PK
Myelodysplastic syndromes (MDS) represent a spectrum of senescence-dependent, hematopoietic stem cell disorders1 with dysplastic cytological features, ineffective hematopoiesis, and a propensity for transformation into acute myeloid leukemia. 2 Response biomarkers to inform delegation of FDA-approved therapies such as the thalidomide analog lenalidomide (Revlimid, Celgene Inc., Warren, NJ, USA) are needed to improve outcomes. High rates of erythroid response to lenalidomide occur in del (5q)-MDS patients because of suppression of haplodeficient phosphatases encoded within the proximal commonly deleted region. 3 A previous report showing that bone marrow lymphoid aggregates appear in association with hematological response implicates immune modulation in this process. 4 Thalidomide, lenalidomide and other structural analogs of this drug class induce potent immune modulation independent of del (5q), with documented activation of T-cells and NK-cells both in vitro and in vivo in multiple myeloma and chronic lymphocytic leukemia. 5--7 In an effort to understand how lenalidomide’s immunomodulatory activity may be linked to hematological response in MDS, we evaluated T-cell activity before and after lenalidomide treatment in vitro, and examined in vivo immune correlation related to hematological response based on International Working Group 2000 criteria. For this analysis, 100 patients with pathologically defined MDS were consented at Moffitt Cancer Center to evaluate immune responses. A total of 13 of these were low-risk, treated with lenalidomide, and had samples collected before and after treatment. Blood samples from an additional five patients with only lenalidomide pretreatment samples available were used for in vitro experiments, but did not contribute to hematological response analysis. Clinical characteristics and lenalidomide responses are shown in Supplementary Table 1. There was no difference between responders (R) and nonresponders (NR) with regard to international prognostic score, World Health Organization classification or age (P ¼ 0.224).
