Nivolumab and ipilimumab are associated with distinct immune landscape changes and response-associated immunophenotypes

BACKGROUNDThe reshaping of the immune landscape by nivolumab (NIVO) and ipilimumab (IPI) and its relation to patient outcomes is not well described.METHODSWe used high-parameter flow cytometry and a computational platform, CytoBrute, to define immunophenotypes of up to 15 markers to assess periphera...

Full description

Saved in:
Bibliographic Details
Published in:JCI insight 2020-06, Vol.5 (11)
Main Authors: Woods, David M, Laino, Andressa S, Winters, Aidan, Alexandre, Jason, Freeman, Daniel, Rao, Vinay, Adavani, Santi S, Weber, Jeffery S, Chattopadhyay, Pratip K
Format: Article
Language:English
Subjects:
Antigens, Differentiation - immunology
Clinical Medicine
Female
Flow Cytometry
Humans
Immunophenotyping
Ipilimumab - administration & dosage
Male
Melanoma - drug therapy
Melanoma - immunology
Melanoma - pathology
Neoplasm Metastasis
Nivolumab - administration & dosage
T-Lymphocytes - immunology
T-Lymphocytes - pathology
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:BACKGROUNDThe reshaping of the immune landscape by nivolumab (NIVO) and ipilimumab (IPI) and its relation to patient outcomes is not well described.METHODSWe used high-parameter flow cytometry and a computational platform, CytoBrute, to define immunophenotypes of up to 15 markers to assess peripheral blood samples from metastatic melanoma patients receiving sequential NIVO > IPI or IPI > NIVO (Checkmate-064).RESULTSThe 2 treatments were associated with distinct immunophenotypic changes and had differing profiles associated with response. Only 2 immunophenotypes were shared but had opposing relationships to response/survival. To understand the impact of sequential treatment on response/survival, phenotypes that changed after the initial treatment and differentiated response in the other cohort were identified. Immunophenotypic changes occurring after NIVO were predominately associated with response to IPI > NIVO, but changes occurring after IPI were predominately associated with progression after NIVO > IPI. Among these changes, CD4+CD38+CD39+CD127-GARP- T cell subsets were increased after IPI treatment and were negatively associated with response/survival for the NIVO > IPI cohort.CONCLUSIONCollectively, these data suggest that the impact of IPI and NIVO on the immunophenotypic landscape of patients is distinct and that the impact of IPI may be associated with resistance to subsequent NIVO therapy, consistent with poor outcomes in the IPI > NIVO cohort of Checkmate-064.
ISSN:2379-3708
2379-3708
DOI:10.1172/jci.insight.137066