Computational algorithm-driven evaluation of monocytic myeloid-derived suppressor cell frequency for prediction of
Shigehisa Kitano1, Michael A Postow2, Carly G K Ziegler3
1Department of Experimental Therapeutics, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Tsukiji, Tokyo, Japan;
Insights
A new computational method accurately quantifies monocytic myeloid-derived suppressor cells (m-MDSC). Higher pretreatment m-MDSC levels in melanoma patients predict better survival with ipilimumab therapy.
Area of Science:
- Immunology
- Computational Biology
- Oncology
Background:
- Myeloid-derived suppressor cells (MDSC) modulate immune responses and T-cell activity.
- Accurate quantification of MDSC subsets, like monocytic MDSC (m-MDSC), is crucial for their use as biomarkers.
- Current methods for m-MDSC assessment lack standardization, hindering clinical application.
Purpose of the Study:
- To develop and validate a computational algorithm for standardized m-MDSC quantification.
- To investigate the association between pretreatment m-MDSC levels and patient outcomes in melanoma treated with ipilimumab.
- To explore the relationship between m-MDSC frequency and T-cell responses post-ipilimumab therapy.
Main Methods:
- Development of a computational algorithm for analyzing whole blood and cryopreserved samples to determine m-MDSC quantity.
- Application of the algorithm to samples from melanoma patients and healthy donors.
- Correlation analysis of m-MDSC frequencies with overall survival and CD8(+) T-cell expansion in patients receiving ipilimumab.
Main Results:
- The algorithm-driven analysis provided a standardized method for m-MDSC quantification, reducing variability.
- Melanoma patients exhibited different m-MDSC frequency distributions compared to healthy donors.
- Melanoma patients with pretreatment m-MDSC frequencies below 14.9% had significantly longer overall survival after ipilimumab treatment.
- m-MDSC frequencies were inversely correlated with CD8(+) T-cell expansion following ipilimumab therapy.
Conclusions:
- Algorithm-driven analysis offers a reproducible method for quantifying peripheral blood m-MDSCs.
- Pretreatment m-MDSC levels may serve as a predictive biomarker for ipilimumab therapy response in melanoma.
- Further validation of peripheral blood m-MDSCs as a biomarker across various diseases is warranted.
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 patients with melanoma identifies differing frequency distribution of m-MDSC relative to that in healthy donors. Patients with a pretreatment m-MDSC frequency outside a preliminary definition of healthy donor 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 were inversely correlated with peripheral CD8(+) T-cell expansion following ipilimumab. Algorithm-driven analysis may enable not only development of a novel pretreatment biomarker for ipilimumab therapy, but also prospective validation of peripheral blood m-MDSCs as a biomarker in multiple disease settings.
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