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 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.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | OncoTarget |
| Vol/bind | 8 |
| Udgave nummer | 16 |
| Sider (fra-til) | 27062-27074 |
| ISSN | 1949-2553 |
| DOI | |
| Status | Udgivet - 2017 |