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01-11-2020 | Melanoma | Original Article

In vitro 4-1BB stimulation promotes expansion of CD8⁺ tumor-infiltrating lymphocytes from various sarcoma subtypes

Authors: Morten Nielsen, Anders Krarup-Hansen, Dorrit Hovgaard, Michael Mørk Petersen, Anand Chainsukh Loya, Marie Christine Wulff Westergaard, Inge Marie Svane, Niels Junker

Published in: Cancer Immunology, Immunotherapy | Issue 11/2020

Abstract

Tumor-specific tumor-infiltrating lymphocytes (TILs) can be in vitro expanded and have the ability to induce complete and durable tumor regression in some patients with melanoma following adoptive cell therapy (ACT). In this preclinical study, we investigated the feasibility of expanding TIL from sarcomas, as well as performing functional in vitro analyses on these. TILs were expanded in vitro by the use of IL2 stimulation with or without the addition of 4-1BB and CD3 antibodies. Phenotypical and functional analyses were mainly performed by flow cytometry. TILs were expanded from 25 of 28 (89%) tumor samples from patients with 9 different sarcoma subtypes. TILs were predominantly αβ T-cells of effector memory subtype with CD4⁺ dominance. In particular, CD8⁺ TIL highly expressed LAG3 and to a lesser degree PD-1 and BTLA. In total, 10 of 20 TIL cultures demonstrated in vitro recognition of autologous tumor. In some cases, the fraction of tumor-reactive T cells was more than 20%. 4-1BB stimulation augmented expansion kinetics and favored CD8⁺ occurrence. In conclusion, TIL expansion from sarcoma is feasible and expanded TILs highly express LAG3 and comprise multifunctional tumor-reactive T-cells.

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Title: In vitro 4-1BB stimulation promotes expansion of CD8+ tumor-infiltrating lymphocytes from various sarcoma subtypes
Authors: Morten Nielsen
Anders Krarup-Hansen
Dorrit Hovgaard
Michael Mørk Petersen
Anand Chainsukh Loya
Marie Christine Wulff Westergaard
Inge Marie Svane
Niels Junker
Publication date: 01-11-2020
Publisher: Springer Berlin Heidelberg
Keywords: Melanoma
Melanoma
Sarcoma
Published in: Cancer Immunology, Immunotherapy / Issue 11/2020
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-020-02568-x

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