Journal article
Influence of ipilimumab on expanded tumour derived T cells from patients with metastatic melanoma
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.
Language: | English |
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Publisher: | Impact Journals LLC |
Year: | 2017 |
Pages: | 27062-27074 |
ISSN: | 19492553 |
Types: | Journal article |
DOI: | 10.18632/oncotarget.16003 |
ORCIDs: | 0000-0002-1983-5222 , 0000-0002-9451-6037 and Hadrup, Sine Reker |
Adult Aged Antineoplastic Agents, Immunological Antineoplastic Agents, Immunological/pharmacology Antineoplastic Combined Chemotherapy Protocols Antineoplastic Combined Chemotherapy Protocols/adverse effects Biomarkers CTLA-4 CTLA-4 Antigen CTLA-4 Antigen/antagonists & inhibitors CTLA4 protein, human Female Humans Immunomodulation Immunomodulation/drug effects Ipilimumab Ipilimumab/pharmacology Lymphocyte Activation Lymphocyte Activation/drug effects Lymphocytes, Tumor-Infiltrating Lymphocytes, Tumor-Infiltrating/drug effects Male Melanoma Melanoma/drug therapy Middle Aged Neoplasm Grading Neoplasm Staging Phenotype T-Cell Antigen Receptor Specificity T-Cell Antigen Receptor Specificity/immunology immunotherapy ipilimumab melanoma tumour infiltrating lymphocyte