OncoImmunology (Feb 2017)

Tumor-infiltrating lymphocytes (TILs) from patients with glioma

  • Zhenjiang Liu,
  • Qingda Meng,
  • Jiri Bartek,
  • Thomas Poiret,
  • Oscar Persson,
  • Lalit Rane,
  • Elena Rangelova,
  • Christopher Illies,
  • Inti Harvey Peredo,
  • Xiaohua Luo,
  • Martin Vijayakumar Rao,
  • Rebecca Axelsson Robertson,
  • Ernest Dodoo,
  • Markus Maeurer

DOI
https://doi.org/10.1080/2162402x.2016.1252894
Journal volume & issue
Vol. 6, no. 2

Abstract

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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.

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