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Published on: November 3, 2018
Immune checkpoints bone marrow expression as the predictor of clinical outcome in myelodysplastic syndrome
Nikolai Tcvetkov1, Artem Gusak1, Elena Morozova1
1R.M. Gorbacheva Memorial Institute of Children Oncology, Hematology and Transplantation, Pavlov First Saint-Petersburg State Medical University, Saint-Petersburg, Russian Federation.
Insights
This study found that immune checkpoint molecule levels in bone marrow biopsies of myelodysplastic syndrome (MDS) patients correlate with disease progression. Higher levels of certain checkpoints, like CD80, are linked to increased risk of MDS progression.
Area of Science:
- Immunology
- Hematology
- Oncology
Background:
- Myelodysplastic syndromes (MDS) are a group of clonal hematopoietic stem cell disorders.
- Immune dysregulation plays a role in MDS pathogenesis and progression.
- Checkpoint molecules are critical regulators of immune responses.
Purpose of the Study:
- To investigate the association between the expression levels of various immune checkpoint molecules in bone marrow biopsies at diagnosis and the clinical course of MDS patients.
- To determine if checkpoint molecule expression impacts overall survival, relapse-free survival, and time-to-progression in MDS.
Main Methods:
- Retrospective analysis of 55 MDS patients diagnosed between 2003 and 2018.
- Detection of checkpoint molecule antigens (PD-1, PD-L1, PD-L2, LAG-3, Gal-9, TIM-3, CD80) in bone marrow biopsies using a specific technique.
- Statistical analysis of the association between antigen expression levels and 3-year survival and progression outcomes.
Main Results:
- High expression of TIM-3 was observed in 100% of MDS cases; moderate Gal-9 expression was common.
- Patients with high CD80 levels showed a significantly higher rate of disease progression (72.9%) compared to those with low CD80 levels (52.1%) (p=0.04).
- Higher overall checkpoint ligand expression was associated with increased 3-year progression incidence (67.2% vs. 33.3%, p=0.059). Expression of CD80, PD-L2, TIM3 correlated with bone marrow blasts and IPSS/IPSS-R risk scores.
Conclusions:
- MDS exhibits heterogeneous expression patterns of immune checkpoint molecules.
- The differential expression of these molecules may influence MDS clinical course and prognosis.
- Further research is warranted to elucidate the role of immune checkpoint heterogeneity in MDS and to develop targeted therapeutic strategies.
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).
Methods And 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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