Abstract 4481: Effect of immune checkpoint blockade on myeloid derived suppressor cell populations in patients with melanoma
Authors: Steven Hao Sun, Brooke Benner, Himanshu Savardekar, Mallory DiVincenzo, David Abood, Andrew Stiff, Megan Duggan, Erin Nagle, John H. Howard, Manisha H. Shah, Kari Kendra, William E. Carson
Journal: Cancer Research (2020)

Abstract Introduction: Myeloid derived suppressor cells (MDSC) are a subset of immature myeloid cells that inhibit innate anti-tumor immunity and promote an immunosuppressive tumor microenvironment. MDSC quantity has been correlated with tumor burden and survival in cancer patients. These cells have the potential to contribute to immune therapy resistance. The purpose of this study was to elucidate the ongoing changes to MDSC populations in patients with advanced melanoma as they receive immune checkpoint therapy. Methods: Patients with melanoma (n=125) were consented to participate in an IRB-approved prospective clinical registry (OSU-13114), and provided blood samples. Samples were drawn at the time of initiation of immune checkpoint therapy (cycle 1), and prior to the beginning of cycles 2 and 3. Samples were then processed using Ficoll and analyzed for MDSC (CD33+/CD11b+/HLA-DRlo/−) and MDSC subsets, monocyte (CD14+, M-MDSC) and granulocytic (CD15+, PMN-MDSC) via flow cytometry. Patient demographics were compiled into a comprehensive database and correlated to the flow cytometry data. Statistical analysis was performed using unpaired and paired t-tests across and within patient cohorts. Results: Total MDSC percentages increased following initiation of immune checkpoint blockade (10 to 25%, p&amp;lt;0.0001). MDSC levels in patients who had complete or partial response began to taper (10% to 26% to 25%), whereas MDSC levels in those who had progressive disease on immunotherapy continued to increase (11% to 16% to 19%). PMN-MDSC significantly decreased after immunotherapy (19% to 10%, p=0.0423). Specifically, patients who received Pembrolizumab had a significant decrease in PMN-MDSC proportion (11% to 2%, p=0.04). A decrease in PMN-MDSC proportion was also noted with Nivolumab (21% to 16%, p=0.097). Patients who had received immune therapy prior to this trial had less PMN-MDSC at baseline (21% vs 12%, p=0.09), and significantly less PMN-MDSC following immune checkpoint blockade (14% vs 2%, p=0.009). Conclusions: MDSC levels initially increase following immune checkpoint blockade, but stabilize in responders and continue to rise in non-responders. The proportion of PMN-MDSC decreases with immune checkpoint blockade, most significantly seen with pembrolizumab. Patients who have been previously treated with immune therapy have a more significant decrease in PMN-MDSC. Citation Format: Steven Hao Sun, Brooke Benner, Himanshu Savardekar, Mallory DiVincenzo, David Abood, Andrew Stiff, Megan Duggan, Erin Nagle, John H. Howard, Manisha H. Shah, Kari Kendra, William E. Carson. Effect of immune checkpoint blockade on myeloid derived suppressor cell populations in patients with melanoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4481.