Computational algorithm-driven evaluation of monocytic myeloid-derived suppressor cell frequency for prediction of clinical outcomes

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 cryopre...

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Bibliographic Details
Published in:	Cancer immunology research Vol. 2; no. 8; p. 812
Main Authors:	Kitano, Shigehisa, Postow, Michael A, Ziegler, Carly G K, Kuk, Deborah, Panageas, Katherine S, Cortez, Czrina, Rasalan, Teresa, Adamow, Mathew, Yuan, Jianda, Wong, Philip, Altan-Bonnet, Gregoire, Wolchok, Jedd D, Lesokhin, Alexander M
Format:	Journal Article
Language:	English
Published:	United States 01-08-2014
Subjects:	Adult Aged Aged, 80 and over Algorithms Antibodies, Monoclonal - therapeutic use Antineoplastic Agents - therapeutic use Female HLA-DR Antigens - immunology Humans Ipilimumab Lipopolysaccharide Receptors - immunology Male Melanoma - drug therapy Melanoma - immunology Middle Aged Myeloid Cells - immunology
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Summary:	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.
ISSN:	2326-6074
DOI:	10.1158/2326-6066.cir-14-0013