Microbial translocation augments the function of adoptively transferred self/tumor-specific CD8⁺ T cells via TLR4 signaling
J. Clin. Invest. Chrystal M. Paulos, et al. 117:2197 doi:10.1172/JCI32205 [Go to this article.]

Figure 4
TLR4 signaling triggered by TBI improves the effectiveness of ACT therapy. (A) Administration of PMB decreased the tumor treatment effectiveness of TBI. Mice bearing s.c. B16F10 tumors established for 10 days received 5 Gy TBI. One day later, mice received an ACT treatment consisting of adoptive transfer of 10⁶ cultured pmel-1 T cells, rFPhgp100 vaccination, and rhIL-2 or were left untreated. For the duration of the experiment, mice were treated or not with PMB in their water. Data (mean ± SEM; n = 5 per group) are representative of 2 independent experiments. (B and C) The effectiveness of treatment was decreased in irradiated mice genetically deficient in CD14 (B) and TLR4 (C). WT, CD14^–/–, and TLR4^–/– tumor-bearing mice were irradiated and then received the ACT treatment described above or were left untreated. Data (mean ± SEM; n = 5 per group) are representative of 2 independent experiments. (D) Serum from irradiated mice improved treatment when transferred to nonirradiated antibody-lymphodepleted mice. Tumor-bearing mice received 5 Gy TBI or were left unirradiated. Alternatively, mice were depleted of lymphocytes with CD4 and NK antibodies and received 5 × 10⁵ cultured pmel-1 T cells, rFPhgp100 vaccination, and IL-2 1 day later. Mice received serum with translocated LPS or serum removed of LPS with Detoxi-gel beads 1 day after ACT. Data (mean ± SEM; n = 4–5 per group) are representative of 2 independent experiments. ^††P < 0.05, ^‡P < 0.01 versus irradiated treated WT mice (A–C) or recipients of serum with LPS (D).