Effect of Immune Checkpoint Blockade on Myeloid-Derived Suppressor Cell Populations in Patients With Melanoma

Introduction Myeloid-derived suppressor cells (MDSC) are a subset of immature myeloid cells that inhibit anti-tumor immunity and contribute to immune therapy resistance. MDSC populations were measured in melanoma patients receiving immune checkpoint inhibitors (ICI). Methods Patients with melanoma (n=128) provided blood samples at baseline (BL), and before cycles 2 and 3 (BC2, BC3). Peripheral blood mononuclear cells (PBMC) were analyzed for MDSC (CD33(+)/CD11b(+)/HLA- DRlo/-) and MDSC subsets, monocytic (CD14+, M-MDSC), granulocytic (CD15+, PMN-MDSC), and early (CD14-/CD15-, E-MDSC) via flow cytometry. Statistical analysis employed unpaired and paired t-tests across and within patient cohorts Results Levels of MDSC as a percentage of PBMC increased during ICI (BL: 9.2 +/- 1.0% to BC3: 23.6 +/- 1.9%, p<0.0001), and patients who developed progressive disease (PD) had higher baseline MDSC. In patients who had a complete or partial response (CR, PR), total MDSC levels rose dramatically and plateaued (BL: 6.4 +/- 1.4%, BC2: 26.2 +/- 4.2%, BC3: 27.5 +/- 4.4%; p<0.0001), whereas DSC rose less sharply in PD patients (BL: 11.7 +/- 2.1%, BC2: 18.3 +/- 3.1%, BC3: 19.0 +/- 3.2%; p=0.1952). Subset analysis showed that within the expanding MDSC population, PMN-MDSC and E-MDSC levels decreased, while the proportion of M-MDSC remained constant during ICI. In PD patients, the proportion of PMN-MDSC (as a percentage of total MDSC) decreased (BL: 25.1 +/- 4.7%, BC2: 16.1 +/- 5.2%, BC3: 8.6 +/- 1.8%; p=0.0105), whereas a heretofore under-characterized CD14+/CD15+ double positive MDSC subpopulation increased significantly (BL: 8.7 +/- 1.4% to BC3: 26.9 +/- 4.9%; p=0.0425). Conclusions MDSC levels initially increased significantly in responders. PMN-MDSC decreased and CD14+CD15+ MDSC increased significantly in PD patients. Changes in MDSC levels may have prognostic value in ICI.