Fig. 1
Schematic to illustrate how dual delivery of OX and IND may impact the anti-PDAC immune response. We hypothesized that nano-enabled co-delivery of a chemotherapeutic agent, which provides an ICD stimulus, and IND, which interferes in the IDO pathway, may combine to trigger a robust PDAC immune response. OX (#1) induces an ICD response (#2) in which CRT expression on the dying tumor cell surfaces provides an “eat-me” signal for DC uptake, as well as the release of HMGB-1 and ATP that deliver adjuvant stimuli to DC (#3). Following uptake of the dying tumor cells by DC, their maturation and cross-presentation of endogenous tumor-associated antigens (TAAs) (#4), the recruitment and activation of CD8+ T cells (#5) will lead to granulysin and perforin mediated killing of primary (#6) and metastatic cancer cells (#7). The concomitant delivery of IND-PL (#8) interferes in the IDO metabolic pathway, which can lead to strengthening the ICD effect by interfering in Treg development and overcome other immunomodulatory effects (#9). The ICD pathway also allows the activation of helper and memory T cells, which prevent disease recurrence (#10). Following proof-of-prinipal testing of this scheme, we also discovered that IND syngergistically enhances the ICD effect, providing more than just an additive outcome (#11)
