Blood platelet RNA profiles do not enable for nivolumab response prediction at baseline in patients with non-small cell lung cancer

Mirte Muller, Myron G. Best, Vincent van der Noort, T. Jeroen N. Hiltermann, Anna-Larissa N. Niemeijer, Edward Post, Nik Sol, Sjors G. J. G. in 't Veld, Tineke Nogarede, Lisanne Visser, Robert D. Schouten, Daan van den Broek, Karlijn Hummelink, Kim Monkhorst, Adrianus J. de Langen, Ed Schuuring, Egbert F. Smit, Harry J. M. Groen, Thomas Wurdinger, Michel M. van den Heuvel

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)

Abstract

BACKGROUND: Anti-PD-(L)1 immunotherapy has emerged as a promising treatment approach for non-small cell lung cancer (NSCLC), though the response rates remain low. Pre-treatment response prediction may improve patient allocation for immunotherapy. Blood platelets act as active immune-like cells, thereby constraining T-cell activity, propagating cancer metastasis, and adjusting their spliced mRNA content. OBJECTIVE: We investigated whether platelet RNA profiles before start of nivolumab anti-PD1 immunotherapy may predict treatment responses. METHODS: We performed RNA-sequencing of platelet RNA samples isolated from stage III-IV NSCLC patients before treatment with nivolumab. Treatment response was scored by the RECIST-criteria. Data were analyzed using a predefined thromboSeq analysis including a particle-swarm-enhanced support vector machine (PSO/SVM) classification algorithm. RESULTS: We collected and processed a 286-samples cohort, separated into a training/evaluation and validation series and subjected those to training of the PSO/SVM-classification algorithm. We observed only low classification accuracy in the 107-samples validation series (area under the curve (AUC) training series: 0.73 (95% -CI: 0.63-0.84, n = 88 samples), AUC evaluation series: 0.64 (95% -CI: 0.51-0.76, n = 91 samples), AUC validation series: 0.58 (95% -CI: 0.45-0.70, n = 107 samples)), employing a five-RNAs biomarker panel. CONCLUSIONS: We concluded that platelet RNA may have minimally discriminative capacity for anti-PD1 nivolumab response prediction, with which the current methodology is insufficient for diagnostic application.
Original languageEnglish
Pages (from-to)S327-S340
JournalTumor Biology
Volume46
Issue numbers1
DOIs
Publication statusPublished - 19 Mar 2024

Keywords

  • Blood platelets
  • RNA-sequencing
  • immunotherapy
  • nivolumab

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