title: Tumor-infiltrating lymphocytes (TILs) from patients with glioma.
abstract: Tumor-infiltrating lymphocytes (TILs) may represent a viable source of T cells for the biological treatment of patients with gliomas. Glioma tissue was obtained from 16 patients, tumor cell lines were established, and TILs were expanded in 16/16 cases using a combination of IL-2/IL-15/IL-21. Intracellular cytokine staining (ICS, IL-2, IL-17, TNFα and IFNγ production) as well as a cytotoxicity assay was used to detect TIL reactivity against autologous tumor cells or shared tumor-associated antigens (TAAs; i.e., NY-ESO-1, Survivin or EGFRvIII). TILs were analyzed by flow cytometry, including T-cell receptor (TCR) Vβ family composition, exhaustion/activation and T-cell differentiation markers (CD45RA/CCR7). IL-2/IL-15/IL-21 expanded TILs exhibited a mixture of CD4+, CD8+, as well as CD3+CD4-CD8-T cells with a predominant central memory CD45RA-CCR7+phenotype. TIL showed low frequencies of T cells testing positive for PD-1, TIM-3 and CTLA-4. LAG3 tested positive in up to 30% of CD8+TIL, with low (1.25%) frequencies in CD4+T cells. TIL cultures exhibited preferential usage of Vβ families and recognition of autologous tumor cells defined by cytokine production and cytotoxicity. IL-2/IL-15/IL-21 expanded TILs represent a viable source for the cellular therapy of patients with gliomas.
authors.affiliation: Therapeutic Immunology Unit, Department of Laboratory Medicine, Karolinska Institutet , Stockholm, Sweden.
authors.forename: Zhenjiang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Therapeutic Immunology Unit, Department of Laboratory Medicine, Karolinska Institutet , Stockholm, Sweden.
authors.forename: Qingda
authors.initials: Q
authors.lastname: Meng
authors.affiliation: Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden; Department of Clinical Neuroscience, Section for Neurosurgery, Karolinska Institutet, Stockholm, Sweden; Department of Neurosurgery, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Jiri
authors.initials: J
authors.lastname: Bartek
authors.affiliation: Therapeutic Immunology Unit, Department of Laboratory Medicine, Karolinska Institutet , Stockholm, Sweden.
authors.forename: Thomas
authors.initials: T
authors.lastname: Poiret
authors.affiliation: Department of Neurosurgery, Karolinska University Hospital , Stockholm, Sweden.
authors.forename: Oscar
authors.initials: O
authors.lastname: Persson
authors.affiliation: Therapeutic Immunology Unit, Department of Laboratory Medicine, Karolinska Institutet , Stockholm, Sweden.
authors.forename: Lalit
authors.initials: L
authors.lastname: Rane
authors.affiliation: Department of Clinical Science, Intervention and Technology, Karolinska Hospital , Stockholm, Sweden.
authors.forename: Elena
authors.initials: E
authors.lastname: Rangelova
authors.affiliation: Department of Neurosurgery, Karolinska University Hospital , Stockholm, Sweden.
authors.forename: Christopher
authors.initials: C
authors.lastname: Illies
authors.affiliation: Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden; Department of Clinical Neuroscience, Section for Neurosurgery, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Inti Harvey
authors.initials: IH
authors.lastname: Peredo
authors.affiliation: Therapeutic Immunology Unit, Department of Laboratory Medicine, Karolinska Institutet , Stockholm, Sweden.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Luo
authors.affiliation: Therapeutic Immunology Unit, Department of Laboratory Medicine, Karolinska Institutet , Stockholm, Sweden.
authors.forename: Martin Vijayakumar
authors.initials: MV
authors.lastname: Rao
authors.affiliation: Therapeutic Immunology Unit, Department of Laboratory Medicine, Karolinska Institutet , Stockholm, Sweden.
authors.forename: Rebecca Axelsson
authors.initials: RA
authors.lastname: Robertson
authors.affiliation: Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden; Department of Clinical Neuroscience, Section for Neurosurgery, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ernest
authors.initials: E
authors.lastname: Dodoo
authors.affiliation: Therapeutic Immunology Unit, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; Center for Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Markus
authors.initials: M
authors.lastname: Maeurer
keywords: Brain tumor; TIL; cellular therapy; cytokines; glioma