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.
| Original language | English |
|---|---|
| Journal | OncoTarget |
| Volume | 8 |
| Issue number | 16 |
| Pages (from-to) | 27062-27074 |
| ISSN | 1949-2553 |
| DOIs | |
| Publication status | Published - 2017 |
Keywords
- Adult
- Aged
- Antineoplastic Agents, Immunological/pharmacology
- Antineoplastic Combined Chemotherapy Protocols/adverse effects
- Biomarkers
- CTLA-4 Antigen/antagonists & inhibitors
- Female
- Humans
- Immunomodulation/drug effects
- Ipilimumab/pharmacology
- Lymphocyte Activation/drug effects
- Lymphocytes, Tumor-Infiltrating/drug effects
- Male
- Melanoma/drug therapy
- Middle Aged
- Neoplasm Grading
- Neoplasm Staging
- Phenotype
- T-Cell Antigen Receptor Specificity/immunology