Tumor-associated myeloid derived suppressor cells of granulocytic nature as a potential biomarker for prognostication of response in treatment of diffuse large cell lymphoma.

Abstract

e19040 Background: NHL is a type of lymphoma either B or T cell origin. However, 85% is of B cell type, especially diffuse large B cell lymphoma (DLBCL) with CD20+ in nature. Standard of care of CD20+DLBCL is R-CHOP 6 to 8 cycles and 66% patients generally respond to this treatment. Remaining 34% is still unresponsive to R-CHOP. Thus, establishment of a biomarker is required to intensify the treatment.Out of different scope of biomarker development, alterations in immune cellular components within tumor microenvironment may be tried as a potential biomarker to assess the possibility of occurrence of residual disease and relapse within 2 years for the DLBCL patients with 6-8 cycles of R-CHOP. Methods: 51 of selected pt.CD20+ DLBCL were treated with 6-8 cycles of R-CHOP and included in the present study. A panel of immune cells CD4+, CD8+ T cells, CD4+CD25+FoxP3 regulatory T cells, CD33+CD11b+CD14-/+ MDSCs and CD8+CD45RO+ Memory T cells were studied by flow-cytometry at different phases of treatment. Results: Within 51selected patients, 9 were disease free and 11patients exhibited stable disease for 2years (stable, non-relapsed, n = 20) following the completion of treatment. Rest of the patients (n = 31) showed relapse in different time periods within 2 years. Among several immune cells, CD33+CD11b+MDSCs were remarkably elevated in high grade residual and relapsed DLBCL patients compared to non-relapsed patients and normal healthy individuals. CD33+CD14- granulocytic, but not CD33+CD14+ monocytic MDSCs are mostly increased in relapsed patients than those having stable disease. CD4+CD25+FoxP3 regulatory T cells are also elevated in relapsed DLBCL patients, but increment is not comparable as MDSCs. No significant alteration was noticed in CD4+ and CD8+ T cells. Among relapsed patients CD8+CD45RO+ Memory T cells are increased, those are mostly corrupted in nature. Conclusions: Observed correlation between increased granulocytic MDSCs with the occurrence of residual disease and/or relapse suggests granulocytic MDSCs might be a potential biomarker for prediction of residual and relapse for DLBCL patients.