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. 2020 May 20;8(1):e000204. doi: 10.1136/jitc-2019-000204

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© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See https://creativecommons.org/licenses/by/4.0/.

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Stratification analyses on response to anti-PD-1 therapy in metastatic cutaneous melanoma. (A) HiRIEF LC-MS/MS heat map of the 84 proteins with a statistically significant change (log2-FC) in plasma protein levels during treatment in the subgroup of anti-PD-1-R, with corresponding changes during treatment in anti-PD-1-NR and patients treated with MAPKis. All comparisons were between trm and pre-trm matching plasma proteomes in the corresponding subgroup, using a paired t test at α=0.05. Some proteins that had a statistically significant log2-FC in plasma levels in anti-PD-1-R had a statistically significant change in anti-PD-1-NR and in patients treated with MAPKis (marked with an *). (B) Heat map on statistically significant change in protein plasma levels during treatment in anti-PD-1-R based on PEA data, with corresponding changes during treatment in anti-PD-1-NR and in patients treated with MAPKis. Although only a certain proportion of the proteins that had a statistically significant log2-FC in plasma levels in anti-PD-1-R had a statistically significant change in patients treated with MAPKis (here marked with a *), the size of the log2-FC indicates that some of the findings were not statistically significant due to the small sample sizes in the anti-PD-1-NR. This is supported by the observations in PD-1 log2-FC in anti-PD-1-R and anti-PD-1-NR (C). (D) Map of proteins with a change in plasma levels during treatment in anti-PD-1-R, which had an involvement in immune biological processes according to GO terms (HiRIEF LC-MS/MS and PEA data). Response to treatment included CR, PR, and SD. CR, complete response; HiRIEF LC-MS/MS, high-resolution isoelectric focusing liquid chromatography–mass spectrometry; GO, gene ontology; ICIs, immune checkpoint inhibitors; ICIs-NRs, patients who were treated with anti-PD-1 ICIs and had no response to treatment (anti-PD-1-NR); ICIs-R, patients who were treated with anti-PD-1 ICIs and responded to treatment (anti-PD-1-R); log2-FC, log2-fold-change; MAPKis, mitogen-activated protein kinase inhibitors; PD-1, programmed cell death protein 1; PEA, proximity extension assays; PR, partial response; pre-trm, pre-treatment; SD, stable disease; trm, after the first treatment cycle.