IFN-γ- and IL-17-producing CD8+ T (Tc17-1) cells in combination with poly-ICLC and peptide vaccine exhibit antiglioma activity.

Abstract

BACKGROUND:

While adoptive transfer of T-cells has been a major medical breakthrough for patients with B cell malignancies, the development of safe and effective T-cell-based immunotherapy for central nervous system (CNS) tumors, such as glioblastoma (GBM), still needs to overcome multiple challenges, including effective homing and persistence of T-cells. Based on previous observations that interleukin (IL)-17-producing T-cells can traffic to the CNS in autoimmune conditions, we evaluated CD8+ T-cells that produce IL-17 and interferon-γ (IFN-γ) (Tc17-1) cells in a preclinical GBM model.

METHODS:

We differentiated Pmel-1 CD8+ T-cells into Tc17-1 cells and compared their phenotypic and functional characteristics with those of IFN-γ-producing CD8+ T (Tc1) and IL-17-producing CD8+ T (Tc17) cells. We also evaluated the therapeutic efficacy, persistence, and tumor-homing of Tc17-1 cells in comparison to Tc1 cells using a mouse GL261 glioma model.

RESULTS:

In vitro, Tc17-1 cells demonstrated profiles of both Tc1 and Tc17 cells, including production of both IFN-γ and IL-17, although Tc17-1 cells demonstrated lesser degrees of antigen-specific cytotoxic activity compared with Tc1 cells. In mice-bearing intracranial GL261-Quad tumor and treated with temozolomide, Tc1 cells, but not Tc17-1, showed a significant prolongation of survival. However, when the T-cell transfer was combined with poly-ICLC and Pmel-1 peptide vaccine, both Tc1 and Tc17-1 cells exhibited significantly prolonged survival associated with upregulation of very late activation antigen-4 on Tc17-1 cells in vivo. Glioma cells that recurred following the therapy lost the susceptibility to Pmel-1-derived cytotoxic T-cells, indicating that immuno-editing was a mechanism of the acquired resistance.

CONCLUSIONS:

Tc17-1 cells were equally effective as Tc1 cells when combined with poly-ICLC and peptide vaccine treatment.

• Authors: Takayuki Ohkuri, Akemi Kosaka, Maki Ikeura, Andres M Salazar, Hideho Okada
• Journal: Journal for immunotherapy of cancer (J Immunother Cancer) Vol. 9 Issue 6 (06 2021) ISSN: 2051-1426 [Electronic] England
• PMID: 34193567 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Chemical References

• Interleukin-17
• Vaccines, Subunit
• Polylysine
• poly ICLC
• Interferon-gamma
• Carboxymethylcellulose Sodium
• Poly I-C

Topics

• CD8-Positive T-Lymphocytes (metabolism)
• Carboxymethylcellulose Sodium (analogs & derivatives, metabolism)
• Glioma (therapy)
• Humans
• Interferon-gamma (metabolism)
• Interleukin-17 (metabolism)
• Poly I-C (metabolism)
• Polylysine (analogs & derivatives, metabolism)
• Vaccines, Subunit (therapeutic use)