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

// Jon Bjoern 1, 2 , Rikke Lyngaa 3, 1 , Rikke Andersen 1, 2 , Lisbet Holmich Rosenkrantz 4 , Sine Reker Hadrup 3, 1 , Marco Donia 1, 2 , Inge Marie Svane 1, 2 1 Center for Cancer Immune Therapy, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark 2 Department of Oncology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark 3 Section for Immunology and Vaccinology, Technical University of Denmark, Copenhagen, Denmark 4 Department of Plastic Surgery, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark Correspondence to: Inge Marie Svane, email: inge.marie.svane@regionh.dk Keywords: melanoma, tumour infiltrating lymphocyte, ipilimumab, CTLA-4, immunotherapy Received: June 06, 2016      Accepted: February 20, 2017      Published: March 08, 2017 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 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.