Skip to main content
Figure 3 | Journal of Translational Medicine

Figure 3

From: Dual effects of a targeted small-molecule inhibitor (cabozantinib) on immune-mediated killing of tumor cells and immune tumor microenvironment permissiveness when combined with a cancer vaccine

Figure 3

Combining cabozantinib with a cancer vaccine improves antigen-specific immune responses in CEA-Tg C57BL/6 mice. (A) Schema of combination therapy study (n =9). (B) To evaluate Treg function, Tregs (CD3+CD4+CD25+FoxP3+) were isolated from spleens and cocultured with CD4+ T cells from naïve mice, APCs (allogeneic splenocytes irradiated with 30 Gy), and soluble anti-CD3 for 72 h. Control wells containing Tregs, APCs, and anti-CD3 without CD4+ T cells were used to determine the background level of Treg proliferation. Control wells containing CD4+ T cells, APCs, and anti-CD3 without Tregs were used to determine the background level of CD4+ T-cell proliferation. Error bars indicate mean ± SEM. Statistical analyses were done by Student's t test. * = P <0.01 relative to CD4+ T-cell proliferation in the presence of Tregs from untreated mice; n.s. indicates no significant difference between the proliferation of CD4+ T cells in the absence of Tregs or in the presence of Tregs from mice treated with combination therapy. (C, D) To evaluate CD8+ T-cell responses, harvested splenocytes were incubated with CEA peptide (1 μg/mL) for 7 days. Lymphocytes were then restimulated with fresh, irradiated, naïve splenocytes and 1 μg/mL of either CEA or HIV-gag peptide for 24 h. Supernatants were collected and analyzed for murine IFN-γ (C) and TNF-α (D) using a cytometric bead array. Nonspecific cytokine production in response to HIV-gag was subtracted from that induced by the CEA peptide. Error bars indicate mean ± SEM. Statistical analyses were done by Student's t test. * = P <0.05 relative to control and single-agent treatments. Data are representative of 2 independent experiments.

Back to article page