Influence of ipilimumab on expanded tumour derived T cells from patients with metastatic melanoma
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Jon Bjoern1,2, Rikke Lyngaa3,1, Rikke Andersen1,2, Lisbet Rosenkrantz Hölmich4, Sine Reker Hadrup3,1, Marco Donia1,2, Inge Marie Svane1,2
1Center for Cancer Immune Therapy, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark
2Department of Oncology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark
3Section for Immunology and Vaccinology, Technical University of Denmark, Copenhagen, Denmark
4Department of Plastic Surgery, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark
Inge Marie Svane, email: firstname.lastname@example.org
Keywords: melanoma, tumour infiltrating lymphocyte, ipilimumab, CTLA-4, immunotherapy
Received: June 06, 2016 Accepted: February 20, 2017 Published: March 08, 2017
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 naïve 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 naïve phenotype expressing markers related to activation or exhaustion. Additionally, Ipilimumab may increase the frequency of T cells recognizing common tumour associated antigens.
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