Šťastná-Marková Markéta, Hainz Petr, Kryštofová Jitka, Macková Jana, Roubalová Kateřina, Vydra Jan, Němečková Šárka
Transplantation and Intensive Care Unit, Institute of Hematology and Blood Transfusion, Prague, Czech Republic.
Institute of Clinical and Experimental Hematology of the 1st Faculty of Medicine of Charles University, Prague, Czech Republic.
Immunotherapy. 2025 Feb;17(3):185-190. doi: 10.1080/1750743X.2025.2478804. Epub 2025 Mar 18.
This study aimed to examine changes in the repertoire of functional T-cells specific for six leukemia-associated antigens (LAA), including WT1, PRAME, MUC1, CCNA1, NPM1, and NPM1c, during immune reconstitution following allogeneic transplantation of hematopoietic stem cells (HSCT) in patients with acute myeloid leukemia.
PATIENTS & METHODS: LAA-specific T cell response was measured by ELISPOT- IFNγ and intracellular cytokine staining in 47 patients before starting conditioning therapy (baseline) and 7 months after HSCT.
The positive cumulative LAA-specific T cell response before HSCT was associated with a decreased risk of relapse after HSCT. The prevalent genetic aberration - an internal tandem duplication of Fms 3 - related receptor tyrosine kinase, which has been previously implicated in immune escape mechanisms, is presented here for the first time as a factor associated with the absence of an adaptive T cell response against multiple LAAs. T-cell specific responses against wild-type and mutated NPM1 antigens were less frequent in the study cohort and did not correlate with mutations in the NPM1 gene.
Our results showed that the T-cell response to LAA can be reconstituted after HSCT. Measurement of functional pre-transplant T-cell responses against multiple LAAs could help to find patients with an increased risk of relapse.
本研究旨在检测急性髓系白血病患者接受异基因造血干细胞移植（HSCT）后免疫重建过程中，针对六种白血病相关抗原（LAA）（包括WT1、PRAME、MUC1、CCNA1、NPM1和NPM1c）的功能性T细胞库的变化。
在47例患者开始预处理治疗前（基线）和HSCT后7个月，通过ELISPOT-IFNγ和细胞内细胞因子染色检测LAA特异性T细胞反应。
HSCT前LAA特异性T细胞反应阳性累积与HSCT后复发风险降低相关。常见的基因畸变——Fms 3相关受体酪氨酸激酶的内部串联重复，此前已被认为与免疫逃逸机制有关，本文首次提出其为与缺乏针对多种LAA的适应性T细胞反应相关的一个因素。在研究队列中，针对野生型和突变型NPM1抗原的T细胞特异性反应较少见，且与NPM1基因的突变无关。
我们的结果表明，HSCT后可重建针对LAA的T细胞反应。检测移植前针对多种LAA的功能性T细胞反应有助于发现复发风险增加的患者。
