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Fig. 3 | Journal for Immunotherapy of Cancer

Fig. 3

From: Enhancing the discovery and development of immunotherapies for cancer using quantitative and systems pharmacology: Interleukin-12 as a case study

Fig. 3

Evidence of cancer cell-immune cell cross-talk: functional inhibition of IL12 responsiveness in 2D6 cells following co-culture with B16F0 melanoma cells. The response of 2D6 cells to co-culture with B16 melanoma cells (dashed curves; □ + IL12; ×-IL12) compared against 2D6 cells alone (solid curves; Δ + IL12; ○-IL12) in the presence (red curves) or absence (blue curves) of IL12, as reported in [96]. Co-culture of 2D6 with B16F0 cells reduced the level of IL12p70 (a) and viability of 2D6 cells (b). Following an induction period, pSTAT4 activity in (c) and the IFN-γ production by (d) 2D6 cells was inhibited by the presence of B16F0 cells. In panel D, the IFN-γ production, given the observed reduction in cell viability, was predicted using the mechanistic math model of 2D6 response to IL12 (dotted black line [48]). Changes in viability (b), IL12Rβ2 (not shown) and pSTAT4 in 2D6 cells (C - CD45+ events) were measured by flow cytometry. Conditioned media was assayed for IL12p70 (A), IFN-γ (D), TNF-α (not shown), IL-6 (not shown), and IL-10 (not shown) by cytometric bead array

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