Dataset Information

Discovery of efficacy biomarkers for NSCLC with first-line anti-PD-1 immunotherapy by DIA

ABSTRACT: To discover potential plasma biomarkers, we are aiming to explore circulating and tumor-derived proteins related to the efficacy of anti-PD-1 treatment to select the optimal NSCLC patients for immunotherapy via DIA.

ORGANISM(S): Homo Sapiens

SUBMITTER: Yuanlin Song

PROVIDER: PXD031474 | iProX | Mon Feb 07 00:00:00 GMT 2022

REPOSITORIES: iProX

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Publications

Discovery of efficacy biomarkers for non-small cell lung cancer with first-line anti-PD-1 immunotherapy by  data-independent acquisition mass spectrometry.

Chao Yencheng Y Jiang Weipeng W Wang Xiaocen X Wang Xiaoyue X Song Juan J Chen Cuicui C Zhou Jian J Huang Qihong Q Hu Jie J Song Yuanlin Y

Clinical and experimental immunology 20220501 1

First-line immune checkpoint inhibitors (ICIs) have greatly ameliorated outcomes in non-small cell lung cancer (NSCLC). However, approximately a quarter of patients receiving ICIs demonstrate long-term clinical benefit, and the true responders have not been fully clarified by the existing biomarkers. To discover potential biomarkers treatment-related outcomes in plasma, mass spectrometry assay for the data-independent acquisition was analyzed plasma samples collected before the anti-PD-1 treatme ...[more]

PMID: 35348622

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Project description:Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide. Although immune checkpoint inhibitors (ICIs) have demonstrated outstanding clinical efficacy in the treatment of NSCLC patients, ICIs-based therapy has also been associated with a paradoxical acceleration of tumor growth defined as hyperprogressive disease (HPD). In this paper we evaluated distinct plasticity traits in a model of HPD-NSCLC, with the aim of clarifying the mechanisms contributing to ICI resistance that involve IFN-γ and PD-L1. For this purpose, primary cell cultures were established from two stage IV NSCLC samples obtained from a single patient: one, prior to ICI initiation (NSCLC-B, baseline) and the other at the time of radiological evidence of hyperprogression under ICI treatment (NSCLC-H, hyperprogression). Compared to NSCLC-B cells, NSCLC-H cells exhibited a more aggressive in vivo and in vitro behavior, higher MAPK activation and owned the ability to develop tumoroids. The 3500 differentially expressed transcripts, according to whole transcriptome analysis, well described the profound plastic evolution of cells from NSCLC-B to NSCLC-H culture, as well as the increase of CD44 in the NSCLC-H cell line model, in which transcripts of CD44 isoforms lacking the variant domain were abundant. Transcripts of genes involved in the cellular response to IFN-γ were down-modulated in NSCLC-H compared to NSCLC-B, together with CD274. Conversely, an up-regulation of genes related to inflammatory response, including IL1- and IFNGR1, was found. In vitro response to IFN- γ was compromised in both NSCLC-B and NSCLC-H cells, since IFN- γ failed to exert its antiproliferative effect on these cells and to effectively induce PD-L1 expression in 2D-growth assays. Nevertheless, the cytokine induced the activation of both type I and type II IFN-pathway mediators. In addition, treatment with IFN-γ induced NSCLC-H traits in NSCLC-B cells, promoting a striking increase in the number of NSCLC-B 3D-soft agar colonies. Low IFN-γ doses or modulation of PD-L1 contributed to the evolution of NSCLC-B towards NSCLC-H phenotype through the augment of CD44 on cell membrane, cell morphological changes and increased cell growth or sphere formation ability. In conclusion, we report a modulation of plasticity by PD-L1 modulation and IFN-γ in a NSCLC cell culture established from a treatment-naïve patient, who developed HPD under ICI therapy, suggesting an association between NSCLC plasticity and these main actors involved in ICI activity.

Dataset Information

Discovery of efficacy biomarkers for NSCLC with first-line anti-PD-1 immunotherapy by DIA

Publications

Discovery of efficacy biomarkers for non-small cell lung cancer with first-line anti-PD-1 immunotherapy by  data-independent acquisition mass spectrometry.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

Discovery of efficacy biomarkers for NSCLC with first-line anti-PD-1 immunotherapy by DIA

Publications

Discovery of efficacy biomarkers for non-small cell lung cancer with first-line anti-PD-1 immunotherapy by data-independent acquisition mass spectrometry.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Discovery of efficacy biomarkers for non-small cell lung cancer with first-line anti-PD-1 immunotherapy by  data-independent acquisition mass spectrometry.