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

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  1. The effects of targeted immune-regulatory strategies on tumor-specific T-cell responses in vitro

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  2. Evidence of immune elimination, immuno-editing and immune escape in patients with hematological cancer

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  3. Arginase-1-based vaccination against the tumor microenvironment: the identification of an optimal T-cell epitope

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  4. TAM-ing T cells in the tumor microenvironment: implications for TAM receptor targeting

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  5. Tumor-induced escape mechanisms and their association with resistance to checkpoint inhibitor therapy

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  1. Lynch syndrome-associated epithelial ovarian cancer and its immunological profile

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  2. The capacity of CD4+ Vγ9Vδ2 T cells to kill cancer cells correlates with co-expression of CD56

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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.

Original languageEnglish
JournalCancer immunology, immunotherapy
Volume69
Issue number11
Pages (from-to)2179-2191
Number of pages13
ISSN0340-7004
DOIs
Publication statusPublished - Nov 2020

    Research areas

  • 4-1BB Ligand/pharmacology, Adult, Aged, Aged, 80 and over, CD8-Positive T-Lymphocytes/drug effects, Cell Culture Techniques/methods, Female, Humans, Lymphocytes, Tumor-Infiltrating/drug effects, Male, Middle Aged, Sarcoma/immunology, Tumor Cells, Cultured

ID: 61244280