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

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

Authors:	Kitano, S.; Postow, M. A.; Ziegler, C. G. K.; Kuk, D.; Panageas, K. S.; Cortez, C.; Rasalan, T.; Adamow, M.; Yuan, J. D.; Wong, P.; Altan-Bonnet, G.; Wolchok, J. D.; Lesokhin, A. M.
Article Title:	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 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. (C) 2014 AACR.
Keywords:	survival; chemotherapy; ipilimumab; patients; carcinoma; tumor; metastatic melanoma; expansion; correlate; cancer stage; advanced melanoma patients
Journal Title:	Cancer Immunology Research
Volume:	2
Issue:	8
ISSN:	2326-6066
Publisher:	American Association for Cancer Research
Date Published:	2014-08-01
Start Page:	812
End Page:	821
Language:	English
ACCESSION:	WOS:000340036000013
DOI:	10.1158/2326-6066.cir-14-0013
PROVIDER:	wos
PMCID:	PMC4125466
PUBMED:	24844912
Notes:	Article -- Source: Wos