> Detailanzeige

Vroman, Heleen; Balzaretti, Giulia; Belderbos, Robert A; Klarenbeek, Paul L; van Nimwegen, Menno; Bezemer, Koen; Cornelissen, Robin; Niewold, Ilse T G; van Schaik, Barbera D; van Kampen, Antione H; Aerts, Joachim G J V; de Vries, Niek; Hendriks, Rudi W

T cell receptor repertoire characteristics both before and following immunotherapy correlate with clinical response in mesothelioma

Literatur-
verwaltung

Zur
Merkliste

Lösche von
Merkliste

Per Whatsapp teilen

Schließen

Merkliste



Sie können Bookmarks mittels Listen verwalten, loggen Sie sich dafür bitte in Ihr SLUB Benutzerkonto ein.
  • Medientyp: E-Artikel
  • Titel: T cell receptor repertoire characteristics both before and following immunotherapy correlate with clinical response in mesothelioma
  • Beteiligte: Vroman, Heleen; Balzaretti, Giulia; Belderbos, Robert A; Klarenbeek, Paul L; van Nimwegen, Menno; Bezemer, Koen; Cornelissen, Robin; Niewold, Ilse T G; van Schaik, Barbera D; van Kampen, Antione H; Aerts, Joachim G J V; de Vries, Niek; Hendriks, Rudi W
  • Erschienen: BMJ, 2020
  • Erschienen in: Journal for ImmunoTherapy of Cancer, 8 (2020) 1, Seite e000251
  • Sprache: Englisch
  • DOI: 10.1136/jitc-2019-000251
  • ISSN: 2051-1426
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: BackgroundMalignant pleural mesothelioma (MPM) is a highly lethal malignancy in need for new treatment options. Although immunotherapies have been shown to boost a tumor-specific immune response, not all patients respond and prognostic biomarkers are scarce. In this study, we determined the peripheral blood T cell receptor β (TCRβ) chain repertoire of nine MPM patients before and 5 weeks after the start of dendritic cell (DC)-based immunotherapy.Materials and methodsWe separately profiled PD1+and PD1−CD4+and CD8+T cells, as well as Tregs and analyzed 70 000 TCRβ sequences per patient.ResultsStrikingly, limited TCRβ repertoire diversity and high average clone sizes in total CD3+T cells before the start of immunotherapy were associated with a better clinical response. To explore the differences in TCRβ repertoire prior-DC-therapy and post-DC-therapy, for each patient the TCRβ clones present in the total CD3+T cell fractions were classified into five categories, based on therapy-associated frequency changes: expanding, decreasing, stable, newly appearing and disappearing clones. Subsequently, the presence of these five groups of clones was analyzed in the individual sorted T cell fractions. DC-therapy primarily induced TCRβ repertoire changes in the PD1+CD4+and PD1+CD8+T cell fractions. In particular, in the PD1+CD8+T cell subpopulation we found high frequencies of expanding, decreasing and newly appearing clones. Conversion from a PD1−to a PD1+phenotype was significantly more frequent in CD8+T cells than in CD4+T cells. Hereby, the number of expanding PD1+CD8+T cell clones—and not expanding PD1+CD4+T cell clones following immunotherapy positively correlated with overall survival, progression-free survival and reduction of tumor volume.ConclusionWe conclude that the clinical response to DC-mediated immunotherapy is dependent on both the pre-existing TCRβ repertoire of total CD3+T cells and on therapy-induced changes, in particular expanding PD1+CD8+T cell clones. Therefore, TCRβ repertoire profiling in sorted T cell subsets could serve as predictive biomarker for the selection of MPM patients that benefit from immunotherapy.Trial registration numberNCT02395679.
  • Zugangsstatus: Freier Zugang