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Tumor Transplantation for Assessing the Dynamics of Tumor-Infiltrating CD8+ T Cells in Mice
Published on: June 12, 2021
Type 17 CD8+ T cells display enhanced antitumor immunity.
Christian S Hinrichs1, Andrew Kaiser, Chrystal M Paulos
1National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.
Blood
|May 28, 2009
Summary
Engineered Interleukin-17 (IL-17)-producing CD8(+) T cells, initially less cytotoxic, effectively mediated tumor regression after adoptive transfer. These cells converted to potent anti-tumor effectors, enhancing cancer immunotherapy potential.
Area of Science:
- Immunology
- Cancer Biology
- Cell Therapy
Background:
- Interleukin-17 (IL-17)-secreting CD8(+) T cells are poorly understood.
- Their role in cancer immunotherapy is currently unknown.
Purpose of the Study:
- To investigate the potential of IL-17-producing CD8(+) T cells in cancer immunotherapy.
- To characterize the function and behavior of these engineered T cells.
Main Methods:
- CD8(+) T cells were primed under Th17-polarizing conditions to induce IL-17 secretion.
- In vitro characterization of IL-17-producing CD8(+) T cells for Eomes expression and cytolytic differentiation.
- In vivo adoptive transfer studies to evaluate anti-tumor immunity and cell persistence.
Main Results:
- IL-17-producing CD8(+) T cells showed reduced Eomes expression and cytolytic capacity in vitro.
- Upon adoptive transfer, these cells converted to interferon-gamma-producing effectors.
- Significant regression of established tumors was observed, linked to enhanced IL-7R-alpha expression and reduced KLRG1, improving cell persistence.
Conclusions:
- This study presents the first evidence of IL-17-secreting CD8(+) T cells as a viable cancer therapy.
- These findings suggest a novel strategy for improving CD8(+) T cell-based adoptive immunotherapy by leveraging IL-17-producing cells.
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