Prognostic Role of Adaptive Immune Microenvironment in Patients with High-Risk Myelodysplastic Syndromes Treated with 5-Azacytidine
Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Immunohistochemistry (IHC)
2.3. Digital Imaging and Cell Population Scoring
2.4. Statistical Analysis
3. Results
3.1. Lower Densities of Adaptive Immune Cell Subpopulations Characterize the Microenvironment of HR-MDS Compared to Age-Matched Normal Controls
3.2. Higher Densities of CD3+ T Cells and CD4+ Th Cells Correlate with Response to Treatment with 5-AZA
3.3. Immune Cell Densities Can Aid in Response Prediction
3.4. Immune Cell Densities Correlate with Overall Survival
3.5. Lower Densities of Tregs and Plasma Cells Correlate with Increased Leukemia-Free Survival
3.6. Lower Densities of T Cells and Higher Densities of Tregs Correlate with Increased Hazard Ratios of Death and Transformation into AML
3.7. An Immune-IPSS-R Score for Enhanced OS and LFS Prediction
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Patient Characteristics | Groups | No. | Percent | Median (Min–Max) |
---|---|---|---|---|
Sex | Male | 51 | 60.7% | |
Female | 33 | 39.3% | ||
Age (N = 84) | 73 (43–90) | |||
Age groups | ≤70 | 30 | 35.7% | |
>71 | 54 | 64.3% | ||
WHO-defined entities | EB1 | 12 | 18.75% | |
EB2 | 44 | 68.75% | ||
AML | 8 | 12.50% | ||
Performance status (ECOG) | 0–1 | 38 | 84.4% | |
2+ | 7 | 15.6% | ||
Karyotype risk groups | Good | 40 | 61.5% | |
Intermediate | 8 | 12.3% | ||
Poor | 17 | 26.2% | ||
Neutrophils (109/Lt) (N = 64) | 0.95 (0.1–17.76) | |||
Monocytes (109/Lt) (N = 63) | 0.17 (0–11.23) | |||
Lymphocytes (109/Lt) (N = 63) | 1.29 (0.11–5.13) | |||
Lymphocyte (109/Lt) groups | <1.0 | 18 | 28.6% | |
>1.0 | 45 | 71.4% | ||
Ratio lymphocytes/monocytes (N = 61) | 7.64 (0.32–157) | |||
Ratio lymphocytes /neutrophils (N = 62) | 1.15 (0.13–7.6) | |||
Ratio lymphocytes/neutrophils (X-tile) | <0.4 | 9 | 14.5% | |
>0.4 | 53 | 85.5% | ||
Platelets (N = 61) | 70 (8–534) | |||
Feritin (mg/mL) baseline (N = 53) | 440 (34–4255) | |||
Hb (g/dL) (N = 64) | 8.85 (5.9–11.8) | |||
Hb (g/dL) groups | >10 | 13 | 20.3% | |
8–10 | 37 | 57.8% | ||
<8 | 14 | 21.9% | ||
No. of cytopenias (N = 62) | 2 (0–3) | |||
BM blasts (%) (N = 63) | 11 (1–50) | |||
IPSS-R score (N = 60) | 6.0 (4–9.5) | |||
IPSS-R groups | Intermediate | 3 | 5.0% | |
High | 32 | 53.3% | ||
Very High | 25 | 41.7% | ||
LDH (N = 65) | 280 (129–1267) | |||
LDH groups | Normal | 21 | 32.3% | |
Abnormal | 44 | 67.7% | ||
Overall response groups (N = 65) | CR/PR/HI | 20 | 30.8% | |
SD | 29 | 44.6% | ||
PD | 16 | 24.6% | ||
Time of best response (months) (N = 18) | 6 (1–12) | |||
Total cycles of Aza given (N = 57) | 8 (1–49) | |||
Transformation into AML (N = 55) | No | 34 | 61.8% | |
Yes | 21 | 38.2% | ||
Time to AML after Vidaza (N = 55) | 14.2 (0–81.7) | |||
Status (N = 65) | Alive | 18 | 27.7% | |
Dead | 47 | 72.3% | ||
Follow-up OS after Vidaza start (months) (N = 64) | 16.59 (0–88.16) | |||
Follow-up LFS after Vidaza start (months) (N = 54) | 14.07 (0–81.70) |
Parameters | Patients | Controls | p (Mann–Whitney U) |
---|---|---|---|
CD3 (mean/mm2) | 764 | 977 | 0.048 |
CD4 (mean/mm2) | 286 | 376 | 0.143 |
CD8 (mean/mm2) | 477 | 640 | 0.036 |
Foxp3 (mean/mm2) | 11.5 | 32.4 | 0.000 |
CD20 (mean/mm2) | 161 | 308 | 0.009 |
FoxP3/CD3 (%) | 1.64% | 3.42% | 0.000 |
FoxP3/CD8 | 0.025 | 0.052 | 0.001 |
Parameter | CR/PR/HI | SD | PD | p (Kruskal–Wallis) |
---|---|---|---|---|
CD3 (mean/mm2) | 852 | 776 | 647 | 0.018 |
CD4 (mean/mm2) | 344 | 292 | 212 | 0.020 |
Lymphocytes/monocytes | 24 | 10.6 | 5.8 | 0.005 |
Hb (g/dL) | 9.3 | 8.9 | 8.4 | 0.010 |
Time to AML (months) | 34.8 | 19.2 | 8.3 | 0.012 |
OS (months) | 36.6 | 16.1 | 11.6 | 0.001 |
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Tsakiraki, Z.; Spathis, A.; Bouchla, A.; Pouliakis, A.; Vryttia, P.; Panayiotides, I.G.; Pappa, V.; Papageorgiou, S.G.; Foukas, P.G. Prognostic Role of Adaptive Immune Microenvironment in Patients with High-Risk Myelodysplastic Syndromes Treated with 5-Azacytidine. Cancers 2025, 17, 1104. https://doi.org/10.3390/cancers17071104
Tsakiraki Z, Spathis A, Bouchla A, Pouliakis A, Vryttia P, Panayiotides IG, Pappa V, Papageorgiou SG, Foukas PG. Prognostic Role of Adaptive Immune Microenvironment in Patients with High-Risk Myelodysplastic Syndromes Treated with 5-Azacytidine. Cancers. 2025; 17(7):1104. https://doi.org/10.3390/cancers17071104
Chicago/Turabian StyleTsakiraki, Zoi, Aris Spathis, Anthi Bouchla, Abraham Pouliakis, Pinelopi Vryttia, Ioannis G. Panayiotides, Vasiliki Pappa, Sotiris G. Papageorgiou, and Periklis G. Foukas. 2025. "Prognostic Role of Adaptive Immune Microenvironment in Patients with High-Risk Myelodysplastic Syndromes Treated with 5-Azacytidine" Cancers 17, no. 7: 1104. https://doi.org/10.3390/cancers17071104
APA StyleTsakiraki, Z., Spathis, A., Bouchla, A., Pouliakis, A., Vryttia, P., Panayiotides, I. G., Pappa, V., Papageorgiou, S. G., & Foukas, P. G. (2025). Prognostic Role of Adaptive Immune Microenvironment in Patients with High-Risk Myelodysplastic Syndromes Treated with 5-Azacytidine. Cancers, 17(7), 1104. https://doi.org/10.3390/cancers17071104