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

    Bibliographical note

    This article is distributed under the terms of the Creative Commons Attribution License (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.

    Cite this

    Bjørn, J., Lyngaa, R. B., Andersen, R., Rosenkrantz, L. H., Hadrup, S. R., Donia, M., & Svane, I. M. (2017). Influence of ipilimumab on expanded tumour derived T cells from patients with metastatic melanoma. OncoTarget, 8(16), 27062-27074. https://doi.org/10.18632/oncotarget.16003
    Bjørn, Jon ; Lyngaa, Rikke Birgitte ; Andersen, Rikke ; Rosenkrantz, Lisbet Holmich ; Hadrup, Sine Reker ; Donia, Marco ; Svane, Inge Marie. / Influence of ipilimumab on expanded tumour derived T cells from patients with metastatic melanoma. In: OncoTarget. 2017 ; Vol. 8, No. 16. pp. 27062-27074.
    @article{25caf41f89654658b672f62d5d7ff1d3,
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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.",
    author = "Jon Bj{\o}rn and Lyngaa, {Rikke Birgitte} and Rikke Andersen and Rosenkrantz, {Lisbet Holmich} and Hadrup, {Sine Reker} and Marco Donia and Svane, {Inge Marie}",
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    Bjørn, J, Lyngaa, RB, Andersen, R, Rosenkrantz, LH, Hadrup, SR, Donia, M & Svane, IM 2017, 'Influence of ipilimumab on expanded tumour derived T cells from patients with metastatic melanoma', OncoTarget, vol. 8, no. 16, pp. 27062-27074. https://doi.org/10.18632/oncotarget.16003

    Influence of ipilimumab on expanded tumour derived T cells from patients with metastatic melanoma. / Bjørn, Jon; Lyngaa, Rikke Birgitte; Andersen, Rikke; Rosenkrantz, Lisbet Holmich; Hadrup, Sine Reker; Donia, Marco; Svane, Inge Marie.

    In: OncoTarget, Vol. 8, No. 16, 2017, p. 27062-27074.

    Research output: Contribution to journalJournal articleResearchpeer-review

    TY - JOUR

    T1 - Influence of ipilimumab on expanded tumour derived T cells from patients with metastatic melanoma

    AU - Bjørn, Jon

    AU - Lyngaa, Rikke Birgitte

    AU - Andersen, Rikke

    AU - Rosenkrantz, Lisbet Holmich

    AU - Hadrup, Sine Reker

    AU - Donia, Marco

    AU - Svane, Inge Marie

    N1 - This article is distributed under the terms of the Creative Commons Attribution License (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.

    PY - 2017

    Y1 - 2017

    N2 - 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.

    AB - 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.

    U2 - 10.18632/oncotarget.16003

    DO - 10.18632/oncotarget.16003

    M3 - Journal article

    VL - 8

    SP - 27062

    EP - 27074

    JO - OncoTarget

    JF - OncoTarget

    SN - 1949-2553

    IS - 16

    ER -