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 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.
Department of Experimental Therapeutics, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Tsukiji, Tokyo, Japan;
Shigehisa
S
Kitano
Memorial Sloan-Kettering Cancer Center; Weill-Cornell Medical and Graduate Schools; and.
Michael A
MA
Postow
Memorial Sloan-Kettering Cancer Center;
Carly G K
CG
Ziegler
Memorial Sloan-Kettering Cancer Center;
Deborah
D
Kuk
Memorial Sloan-Kettering Cancer Center;
Katherine S
KS
Panageas
Memorial Sloan-Kettering Cancer Center; Ludwig Collaborative and Swim Across America Lab, New York, New York.
Czrina
C
Cortez
Ludwig Center for Cancer Immunotherapy; Memorial Sloan-Kettering Cancer Center; Ludwig Collaborative and Swim Across America Lab, New York, New York.
Teresa
T
Rasalan
Ludwig Center for Cancer Immunotherapy; Memorial Sloan-Kettering Cancer Center;
Mathew
M
Adamow
Ludwig Center for Cancer Immunotherapy; Memorial Sloan-Kettering Cancer Center;
Jianda
J
Yuan
Ludwig Center for Cancer Immunotherapy; Memorial Sloan-Kettering Cancer Center;
Philip
P
Wong
Memorial Sloan-Kettering Cancer Center;
Gregoire
G
Altan-Bonnet
Ludwig Center for Cancer Immunotherapy; Memorial Sloan-Kettering Cancer Center; Weill-Cornell Medical and Graduate Schools; and Ludwig Collaborative and Swim Across America Lab, New York, New York.
Jedd D
JD
Wolchok
Memorial Sloan-Kettering Cancer Center; Weill-Cornell Medical and Graduate Schools; and Ludwig Collaborative and Swim Across America Lab, New York, New York lesokhia@mskcc.org.
Alexander M
AM
Lesokhin
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D000074324:Ipilimumab; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000276:immunology*; D008875:Middle Aged; D022423:Myeloid Cells / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D006684:HLA-DR Antigens; D000074324:Ipilimumab; D018950:Lipopolysaccharide Receptors