Influence of ipilimumab on expanded tumour derived T cells from patients with metastatic melanoma

Jon Bjørn, Rikke Birgitte Lyngaa, Rikke Andersen, Lisbet Holmich Rosenkrantz, Sine Reker Hadrup, Marco Donia, Inge Marie Svane

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    Abstract

    Introduction: Tumour infiltrating lymphocyte (TIL) based adoptive cell therapy (ACT) is a promising treatment for patients with advanced melanoma. Retrospective studies suggested an association between previous treatment with anti-CTLA-4 antibodies and long term survival after subsequent ACT. Thus, we hypothesized that treatment with anti-CTLA-4 antibodies can induce favourable changes to be detected in TILs.Results: Expanded T cells from Ipilimumab treated patients had a higher proportion of cells expressing CD27, intracellular CTLA-4, TIM-3 and LAG-3. In addition, broader and more frequent T cell responses against common tumour antigens were detected in patients treated with Ipilimumab as compared to anti-CTLA-4 naive patients.Materials and methods: Expanded TILs were obtained from patients with advanced melanoma who had received Ipilimumab in the previous six months, or had not received any type of anti-CTLA-4 antibody. T cell specificity and expression of phenotypic and exhaustion markers were scrutinized as well as functional properties.Conclusions: Ipilimumab may induce tumor-infiltration of T cells of a more naive phenotype expressing markers related to activation or exhaustion. Additionally, Ipilimumab may increase the frequency of T cells recognizing common tumour associated antigens.
    Original languageEnglish
    JournalOncoTarget
    Volume8
    Issue number16
    Pages (from-to)27062-27074
    ISSN1949-2553
    DOIs
    Publication statusPublished - 2017

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