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
C2 - 28423678
SN - 1949-2553
VL - 8
SP - 27062
EP - 27074
JO - OncoTarget
JF - OncoTarget
IS - 16
ER -