Tumor-infiltrating lymphocytes (TILs) from patients with glioma

• Published in: Oncoimmunology Vol. 6; no. 2; p. e1252894
• Main Authors: Liu, Zhenjiang, Meng, Qingda, Bartek, Jiri, Poiret, Thomas, Persson, Oscar, Rane, Lalit, Rangelova, Elena, Illies, Christopher, Peredo, Inti Harvey, Luo, Xiaohua, Rao, Martin Vijayakumar, Robertson, Rebecca Axelsson, Dodoo, Ernest, Maeurer, Markus
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01.02.2017; Taylor & Francis Group
• Subjects: Brain tumor; cellular therapy; cytokines; glioma; Original Research; TIL; Brain tumor; glioma; cytokines; cellular therapy; TIL
• ISSN: 2162-402X; 2162-4011; 2162-402X
• DOI: 10.1080/2162402X.2016.1252894

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.