Tumor-Associated Myeloid Derived Suppressor Cells Of Granulocytic Nature As A Potential Biomarker For Prognostication Of Response In Treatment Of Diffuse Large Cell Lymphoma.

30 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: : Selected CD20+ DLBCL patients (n=51) were treated with 6-8 cycles of R-CHOP and included in the present study with their informed consent. A panel of immune cells, like, T (CD4+, CD8+)-cells, regulatory T (CD4+CD25+FoxP3)-cells, MDSCs (CD33+CD11b+CD14-/+), memory T (CD8+CD45RO+)-cells and multidrug resistance (MDR) phenotypes (P-gp, MRP1), were studied by flow-cytometry and RT-PCR at different phases of treatment. Results: Within 51 selected patients, 9 were disease free and 11 patients exhibited stable disease for 2 years following the completion of treatment. Rest of the patients (n=31) showed relapse in different time periods. Among several immune cells studied, 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+ monocytic, but not CD33+CD14-granulocytic MDSCs were mostly increased in relapsed patients than control. Moreover, expression of MDR phenotypic markers was found to be elevated in these relapsed patients. Among relapsed patients CD8+CD45RO+ memory T cells were increased, however, these cells are mostly corrupted in nature. Conclusions: Observed correlation between increased monocytic MDSCs with the occurrence of residual disease and/or relapse suggests monocytic MDSCs might be a potential biomarker for prediction of residual-and-relapsed DLBCL patients.