Figure 9: Model of immunogenic cell injury generating anti-tumor immunity.

Intra-tumoral injection of tumor cells treated ex vivo with DNA-damaging chemotherapy promotes effective DC-mediated T cell priming and expansion when combined with systemic immune checkpoint blockade. Neither cell-free supernatants, the dead cell fraction, nor lysates of the chemotherapy-treated tumor cells generated by three cycles of freeze-thawing, when co-incubated with DC, promoted a T cell IFN-γ response, indicating that some type of active cellular process beyond cytokine secretion from genotoxically injured tumor cells is likely involved. Furthermore, if the DCs and/or T cells were also exposed to the cytotoxic chemotherapy drug, T cell IFN-γ responses were impaired. Consequently, direct intra-tumoral injection of the free chemotherapeutic drug, in combination with systemic ICB administration, was largely ineffective at inducing an anti-tumor immunogenic response.