Contributions
Abstract: PB2078
Type: Publication Only
Background
Several data have been showing that immune-dependent mechanisms might be relevant for the selection, expansion and dominance of dysplastic clone/s in a subgroup of Myelodysplastic (MDS) patients. To date, valuable criteria to identify patients in which a deranged immune response might account for the selection/shaping of the dysplastic precursor/s are still lacking. Immune response is a microsite phenomenon, thus the analysis of the immune effectors in the Bone Marrow (BM) offers a unique possibility to specifically focus the mechanisms underlying the immune-mediated processes likely involved in the selection/expansion of dysplastic clone/s in MDS.
Aims
We previously described that specific alterations of immune profile, as represented by low Treg levels and high expression of CD54 on CD8 effectors in BM, allow the identification of a subgroup of MDS patients in which an immune-mediated pathogenesis of the disease might be inferred. This study aims to confirm and extend these data trying to correlate tolerance control derangement in BM with pathological expansion of T cell effectors in Low Risk MDS patients. Moreover, we address the evaluation of Treg level as a valuable prognostic marker in Low Risk MDS.
Methods
To investigate the occurrence of antigen-dependent clonal expansion of CD4 and CD8 T lymphocytes, we analysed, by flow cytometry, TCR Vb repertoire in BM as compared with peripheral blood in 26 Low Risk patients and healthy donors. To evaluate the prognostic role of BM Treg at diagnosis, we have investigated the occurrence of leukemia evolution and overall survival in our cohort of patients in a minimal 36 month follow up.
Results
Preliminary data confirm that Treg, a key element for cell-mediated tolerance control, show a clustered distribution in BM; moreover, their quantitative defect correlates with the recruitment and the activation of T cell cytotoxic effectors in BM. The analysis of preferential CD4 and CD8 T cell expansion in BM, respect to peripheral blood, reveals the presence of oligoclonal BM expansions of CD8 and CD4 T lymphocytes. Notably, CD8 BM expansions are significantly related to low Treg level (<2% of BM lymphocytes). Moreover, our data indicate that the subgroup of patients with low BM Treg level, at diagnosis, shows significant lower leukemia evolution and death in a minimum 36 month follow up.
Conclusion
These data suggest that BM Treg level may represent a valuable criterion to identify the subgroup of Low Risk MDS patients in which immune-mediated mechanisms are relevant for MDS pathogenesis. A more homogeneous grouping of Low Risk patients will improve clinical management of the disease, hopefully allowing a more effective employment of innovative immune-modulating strategies in MDS.
Session topic: 9. Myelodysplastic syndromes – Biology & Translational Research
Keyword(s): Cytotoxic T cell, Myelodysplasia, T regulatory cells
Abstract: PB2078
Type: Publication Only
Background
Several data have been showing that immune-dependent mechanisms might be relevant for the selection, expansion and dominance of dysplastic clone/s in a subgroup of Myelodysplastic (MDS) patients. To date, valuable criteria to identify patients in which a deranged immune response might account for the selection/shaping of the dysplastic precursor/s are still lacking. Immune response is a microsite phenomenon, thus the analysis of the immune effectors in the Bone Marrow (BM) offers a unique possibility to specifically focus the mechanisms underlying the immune-mediated processes likely involved in the selection/expansion of dysplastic clone/s in MDS.
Aims
We previously described that specific alterations of immune profile, as represented by low Treg levels and high expression of CD54 on CD8 effectors in BM, allow the identification of a subgroup of MDS patients in which an immune-mediated pathogenesis of the disease might be inferred. This study aims to confirm and extend these data trying to correlate tolerance control derangement in BM with pathological expansion of T cell effectors in Low Risk MDS patients. Moreover, we address the evaluation of Treg level as a valuable prognostic marker in Low Risk MDS.
Methods
To investigate the occurrence of antigen-dependent clonal expansion of CD4 and CD8 T lymphocytes, we analysed, by flow cytometry, TCR Vb repertoire in BM as compared with peripheral blood in 26 Low Risk patients and healthy donors. To evaluate the prognostic role of BM Treg at diagnosis, we have investigated the occurrence of leukemia evolution and overall survival in our cohort of patients in a minimal 36 month follow up.
Results
Preliminary data confirm that Treg, a key element for cell-mediated tolerance control, show a clustered distribution in BM; moreover, their quantitative defect correlates with the recruitment and the activation of T cell cytotoxic effectors in BM. The analysis of preferential CD4 and CD8 T cell expansion in BM, respect to peripheral blood, reveals the presence of oligoclonal BM expansions of CD8 and CD4 T lymphocytes. Notably, CD8 BM expansions are significantly related to low Treg level (<2% of BM lymphocytes). Moreover, our data indicate that the subgroup of patients with low BM Treg level, at diagnosis, shows significant lower leukemia evolution and death in a minimum 36 month follow up.
Conclusion
These data suggest that BM Treg level may represent a valuable criterion to identify the subgroup of Low Risk MDS patients in which immune-mediated mechanisms are relevant for MDS pathogenesis. A more homogeneous grouping of Low Risk patients will improve clinical management of the disease, hopefully allowing a more effective employment of innovative immune-modulating strategies in MDS.
Session topic: 9. Myelodysplastic syndromes – Biology & Translational Research
Keyword(s): Cytotoxic T cell, Myelodysplasia, T regulatory cells