Chimeric NKG2D T Cells Require Both T Cell- and Host-Derived Cytokine Secretion and Perforin Expression to Increase Tumor Antigen Presentation and Systemic Immunity
Open Access
- 15 August 2009
- journal article
- research article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 183 (4), 2365-2372
- https://doi.org/10.4049/jimmunol.0900721
Abstract
Treatment of mice bearing established ovarian tumors with T cells expressing chimeric NKG2D receptors (chNKG2D) develop protective host immune responses to tumor Ags. In this study, the mechanisms that chNKG2D T cells require to induce host immunity against ovarian tumors and which of the host immune cells are involved in tumor elimination were determined. Treatment with chNKG2D T cells led to a sustained, increased IFN-γ production by host NK, CD4+, and CD8+ T cells in the spleen and at the tumor site and this continued for many weeks after T cell injection. Tumor Ag presentation was enhanced in chNKG2D T cell-treated mice, and there were greater numbers of tumor-specific T cells at the tumor site and in draining lymph nodes after treatment with chNKG2D T cells. The increase in host cell cytokine secretion and Ag presentation was dependent on chNKG2D T cell-derived perforin, IFN-γ, and GM-CSF. Host immune mechanisms were involved in tumor elimination because inhibition of tumor growth was limited in mice that lacked perforin, IFN-γ, NK cells, or T and B cells (Rag1−/−). There was no role for host-derived GM-CSF or CD1-dependent NKT cells, because mice deficient in these were able to clear tumors as well as treated wild-type B6 mice. In summary, chNKG2D T cells required both cytotoxicity and cytokine secretion as well as the participation of host immune cells for development of a host antitumor immune response and complete efficacy.Keywords
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