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Fig. 1 | Journal for ImmunoTherapy of Cancer

Fig. 1

From: Toll-like receptor agonist therapy can profoundly augment the antitumor activity of adoptively transferred CD8+ T cells without host preconditioning

Fig. 1

Lymphodepletion augments the antitumor activity of transferred CD8+ T cells via depleting host suppressor T cells and activating APCs. a TBI augmented antitumor responses in mice. C57BL6 mice bearing subcutaneous B16F10 tumors established for 8 days received non-myeloablative 5Gy TBI or were not irradiated. One day later, mice received an ACT treatment regimen consisting of the adoptive transfer of 1e6 cultured tumor-reactive pmel-1 CD8+ T cells, fowlpox hgp100 vaccination and hIL-2 or were left untreated (NT). Data (mean +/- SEM, n = 5 mice per group) are representative of 5 independent experiments. PFI vs. 5Gy PFI, **P < .01, ANOVA. b TBI increased the engraftment of infused pmel-1 CD8+ T cells over host CD8+ or host CD4+ T cells relative to non-irradiated mice. Ratios of transferred pmel-1 CD8+ T cells (Vβ13+Ly5.1+) relative to returning host CD8+ and CD4+ T cells are shifted toward pmel-1 CD8+ T cells in irradiated mice. B6 mice were given 5Gy TBI or not followed by the transfer of 1e6 pmel-1 CD8+ T cells (Ly5.1+), fowlpox hgp100 vaccination and hIL-2. Splenocytes obtained 1 week after transfer were simultaneously analyzed for infused pmel-1 CD8+ and reconstituting host cells. c TBI up-regulates costimulatory molecules on host CD11b+CD11chi dendritic cells. Splenic DCs were isolated at 24 h from mice treated with 5Gy TBI or without. The expression of costimulatory molecules (CD86, ICOSL, OX40L and 41BBL) on CD11chi-gated DCs were analyzed by flow cytometry and displayed in histogram form. d TBI depletes endogenous CD4+ and CD8+ T cells and transiently promotes activation of CD11chi dendritic cells. Splenocytes were isolated from 0 and 5Gy irradiated mice 2 days after TBI. Absolute numbers of CD4+, CD8+ and activated CD11b+CD11chiCD86hi DCs in the spleens of TBI and non-irradiated C57BL6 mice were enumerated. Data shown are representative of 2 independent experiments. **P < .01, unpaired t-test

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