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bioRxiv · 10.1101/2020.01.13.905430

Nivolumab and Ipilimumab in Metastatic Melanoma Are Associated with Distinct Immune Landscape Changes and Response-Associated Immunophenotypes

Woods, D. M.·Laino, A. S.·Winters, A. F.·Alexandre, J. M.·Rao, V.·Adavani, S. S.·Weber, J. S.·Chattopadhyay, P. K.
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Abstract

The reshaping of the immune landscape by nivolumab (NIVO) and ipilimumab (IPI) and its relation to patient outcomes is not well-described. We used high-parameter flow cytometry and a novel 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. The two treatments were associated with distinct immunophenotypic changes and had differing profiles associated with response. Only two 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 post-NIVO were predominately associated with response to IPI>NIVO, but changes occurring post-IPI were predominately associated with progression with 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.

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Woods, D. M., Laino, A. S., Winters, A. F., Alexandre, J. M., Rao, V., Adavani, S. S., Weber, J. S., Chattopadhyay, P. K.. 2020-01-16. Nivolumab and Ipilimumab in Metastatic Melanoma Are Associated with Distinct Immune Landscape Changes and Response-Associated Immunophenotypes. https://doi.org/10.1101/2020.01.13.905430

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