Computational Algorithm-Driven Evaluation of Monocytic Myeloid-Derived Suppressor Cell Frequency for Prediction of Clinical Outcomes

Abstract

Evaluation of myeloid-derived suppressor cells (MDSC), a cell type implicated in T-cell suppression, may inform immune status. However, a uniform methodology is necessary for prospective testing as a biomarker. We report the use of a computational algorithm-driven analysis of whole blood and cryopreserved samples for monocytic MDSC (m-MDSC) quantity that removes variables related to blood processing and user definitions. Applying these methods to samples from melanoma patients identifies differing frequency distribution of m-MDSC relative to that in healthy donors (HD). Patients with a pre-treatment m-MDSC frequency outside a preliminary definition of HD range (<14.9%) were significantly more likely to achieve prolonged overall survival following treatment with ipilimumab, an antibody that promotes T-cell activation and proliferation. m-MDSC frequencies inversely correlated with peripheral CD8+ T-cell expansion following ipilimumab. Algorithm-driven analysis may enable not only development of a novel pre-treatment biomarker for ipilimumab therapy, but also prospective validation of peripheral blood m-MDSC as a biomarker in multiple disease settings.

Myeloid Cells and Related Chronic Inflammatory Factors as Novel Predictive Markers in Melanoma Treatment with Ipilimumab

“…In our cohort of patients, we found that a pretreatment moMDSC frequency in nonresponders was slightly higher than in responders. However, in contrast with recent publications (11,28), this elevation was not statistically significant. Furthermore, we observed a significant increase of moMDSC frequencies in nonresponders after the first and second Ipi infusion, whereas in responders, the moMDSC level showed a strong reduction upon the therapy as compared with basal values.…”

Pretreatment Immune Status Correlates with Progression-Free Survival in Chemotherapy-Treated Metastatic Colorectal Cancer Patients

“…Large numbers of MDSCs are a poor prognostic factor for various cancer patients (16)(17)(18)(19)(20). Therefore, we also hypothesized that the quantity of MDSCs might affect the prognosis of patients with MCRC.…”

Transcriptional profiling of whole blood: a rich source of immune biomarkers in cancer

“…Our research is thus in line with reported findings that alterations in peripheral blood suppressor myeloid cell populations correlate with, and are predictive of, response to CTLA-4 blockade. 9 Furthermore, the genes identified in our panel to correlate inversely with survival, CTSD and IRAK3, have established roles in cancer growth and immunosuppression. IRAK3, is primarily expressed by myeloid cells and suppresses toll-like receptor signaling, diminishing the perception of "danger signals" by the immune system.…”