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. Author manuscript; available in PMC: 2020 Dec 8.
Published in final edited form as: Clin Cancer Res. 2020 Feb 4;26(9):2216–2230. doi: 10.1158/1078-0432.CCR-18-3626

Figure 6.

Figure 6.

Potential mechanisms of the full combination treatment using vMyx-IL15Rα-tdTr. The effect of celecoxib on the tumor-infiltrated NK, CD8+ T cells, and Tregs when treated with vMyx-IL15Rα-tdTr virus. C57BL/6J mice were implanted with GL261 NS cells intracranially on day 0, then received 1 μL vMyx-IL15Rα-tdTr virus (2 × 106 pfu) injection and rapamycin with or without celecoxib on day 7 (medication treatment continued until day 12), adoptive transfer of CD8+ T cells on day 9, and TriVax booster on day 10. Mice were euthanized on day 12 and tumor sections were analyzed for presence of NK cells, CD8+ T cells, and Tregs by immunostaining for Ly-49G2 (4D11 antibody), CD8, and Foxp3, respectively. A, Number of infiltrated Ly-49G2+ NK cells, CD8+ T cells, and Foxp3+ Tregs per tumor section for each condition are shown (mean and SEM). There was a significant increase of infiltrated CD8+ T cells and significant decrease of infiltrated Tregs when celecoxib was included in the treatment. *, P < 0.05; **, P < 0.01. B, The ratio of tumor-infiltrated CD8+ T cells over tumor-infiltrated Tregs for each condition. There was a significant increase of the ratio when GL261 NS tumor was treated with vMyx-IL15Rα-tdTr and celecoxib. ****, P < 0.0001. C-F, Infiltration of gliomas by tumor-specific T cells following treatment of mice with oncolytic vMyx-IL15Rα-tdTr, rapamycin, celecoxib, and adoptive transfer of tumor-specific CD8+ T cells. Mice bearing GL261 gliomas were treated with a combination oncolytic virus and immunotherapy and euthanized four days after adoptive T-cell therapy. The right striatum and spleen were dissociated, and cells were analyzed by flow cytometry for CD8 and binding of a GARC-1-Db DimerX to detect tumor-specific T cells. Controls received only a PBS infusion or were untreated non-tumor-bearing mice. C, Total number of CD8+ T cells in spleen. D, Total number of GARC-1–specific CD8+ T cells in spleen. **, P < 0.01. E, Total number of CD8+ T cells in gliomas. *, P < 0.05. F, Total number of GARC-1–specific CD8+ T cells in gliomas. *, P < 0.05.