Analysis of Immune Checkpoint Drug Targets and Tumor Proteotypes in Non-Small Cell Lung Cancer



Liebler, Daniel C, Holzer, Timothy R, Haragan, Alexander ORCID: 0000-0002-9747-563X, Morrison, Ryan D, O’Neill Reising, Leslie, Ackermann, Bradley L, Fill, Jeff A, Schade, Andrew E and Gruver, Aaron M
(2020) Analysis of Immune Checkpoint Drug Targets and Tumor Proteotypes in Non-Small Cell Lung Cancer. Scientific Reports, 10.

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Abstract

New therapeutics targeting immune checkpoint proteins have significantly advanced treatment of non-small cell lung cancer (NSCLC), but protein level quantitation of drug targets presents a critical problem. We used multiplexed, targeted mass spectrometry (MS) to quantify immunotherapy target proteins PD-1, PD-L1, PD-L2, IDO1, LAG3, TIM3, ICOSLG, VISTA, GITR, and CD40 in formalin-fixed, paraffin-embedded (FFPE) NSCLC specimens. Immunohistochemistry (IHC) and MS measurements for PD-L1 were weakly correlated, but IHC did not distinguish protein abundance differences detected by MS. PD-L2 abundance exceeded PD-L1 in over half the specimens and the drug target proteins all displayed different abundance patterns. mRNA correlated with protein abundance only for PD-1, PD-L1, and IDO1 and tumor mutation burden did not predict abundance of any protein targets. Global proteome analyses identified distinct proteotypes associated with high PD-L1-expressing and high IDO1-expressing NSCLC. MS quantification of multiple drug targets and tissue proteotypes can improve clinical evaluation of immunotherapies for NSCLC.

Item Type: Article
Uncontrolled Keywords: Cancer immunotherapy, Mass spretrometry, Non-small-cell lung cancer, Proteomics
Depositing User: Symplectic Admin
Date Deposited: 26 Jun 2020 08:11
Last Modified: 01 Aug 2020 09:27
DOI: 10.1038/s41598-020-66902-0
Related URLs:
URI: http://livrepository.liverpool.ac.uk/id/eprint/3091687