TY - JOUR

T1 - Influence of ipilimumab on expanded tumour derived T cells from patients with metastatic melanoma

AU - Bjoern, Jon

AU - Lyngaa, Rikke

AU - Andersen, Rikke

AU - Rosenkrantz, Lisbet Hölmich

AU - Hadrup, Sine Reker

AU - Donia, Marco

AU - Svane, Inge Marie

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 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.

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 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.

KW - Adult

KW - Aged

KW - Antineoplastic Agents, Immunological/pharmacology

KW - Antineoplastic Combined Chemotherapy Protocols/adverse effects

KW - Biomarkers

KW - CTLA-4 Antigen/antagonists & inhibitors

KW - Female

KW - Humans

KW - Immunomodulation/drug effects

KW - Ipilimumab/pharmacology

KW - Lymphocyte Activation/drug effects

KW - Lymphocytes, Tumor-Infiltrating/drug effects

KW - Male

KW - Melanoma/drug therapy

KW - Middle Aged

KW - Neoplasm Grading

KW - Neoplasm Staging

KW - Phenotype

KW - T-Cell Antigen Receptor Specificity/immunology

U2 - 10.18632/oncotarget.16003

DO - 10.18632/oncotarget.16003

M3 - Journal article

C2 - 28423678

VL - 8

SP - 27062

EP - 27074

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 16

ER -