Analysis of Immune Checkpoint Drug Targets and Tumor Proteotypes in Non-Small Cell Lung Cancer.
Sci Rep
; 10(1): 9805, 2020 06 17.
Article
em En
| MEDLINE
| ID: mdl-32555523
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Sistemas de Liberação de Medicamentos
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Carcinoma Pulmonar de Células não Pequenas
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Inibidores de Checkpoint Imunológico
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Neoplasias Pulmonares
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article