Immune checkpoints bone marrow expression as the predictor of clinical outcome in myelodysplastic syndrome

免疫检查点骨髓表达作为骨髓增生异常综合征临床结果的预测指标

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作者:Nikolai Tcvetkov, Artem Gusak, Elena Morozova, Ivan Moiseev, Vadim Baykov, Maria Barabanshikova, Kirill Lepik, Evgenyi Bakin, Julia Vlasova, Anna Osipova, Ludmila Zubarovskaya, Boris Afanasyev

Aims

In our single-center retrospective study we evaluated whether level of different checkpoint molecules in bone marrow biopsies at diagnosis affect the clinical course of patients with myelodysplastic syndrome (MDS).

Conclusions

Our preliminary study underlined heterogeneous immune checkpoint molecules expression in MDS and warrants further studies to define the role of this heterogeneity and develop optimal treatment approaches.

Results

A consecutive cohort of 55 MDS patients treated in our center from 2003 to 2018 with available bone marrow biopsies at time of diagnosis was studied. We used a technique able to detect the expression of the following antigens: PD-1, PD-L1, PD-L2, LAG-3, Gal-9, TIM-3, CD80. The association between expression level and 3-year overall and relapse-free survival and time-to-progression was analyzed. Intensive expression of TIM-3 was observed in 100% of cases. Also, in most cases, moderate Gal-9 expression was observed. With 3-year follow-up disease progression was seen in 72.9% of patients with high CD80 level and 52.1% of patients with low CD80 level (p=0.04). PD-1, CTLA4 and TIM-3 ligands were co-expressed in the majority of patients. General checkpoint ligand expression level also was associated with increased 3-year incidence of progression: 67.2% of patients with high level of checkpoint ligands progressed, while in the group with low checkpoint ligand expression level progression was observed only in 33.3% of cases (p=0.059). There was an association between the expression of checkpoint molecules CD80, PD-L2, TIM3, the number of bone marrow blasts and risk according to IPSS and IPSS-R scales. Conclusions: Our preliminary study underlined heterogeneous immune checkpoint molecules expression in MDS and warrants further studies to define the role of this heterogeneity and develop optimal treatment approaches.

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