Objective:

To evaluate the therapeutic response to combined targeting of CSF-1R and IDO in pancreatic ductal adenocarcinoma (PDAC) models with differing fibrotic profiles and to assess the context-dependent efficacy of this approach.

Approach:

• Study Models: Utilized two orthotopic PDAC models (KPC4662.5 and Pan02) with distinct stromal compositions and CSF-1R expression levels.
• Therapeutic Strategy: Administered PLX3397 (CSF-1R inhibitor) and IDO-targeting Salmonella to assess their combined effect on tumor burden and immune cell composition.

Key Findings:

• KPC4662.5 tumors exhibited higher fibrosis and CSF-1R expression compared to Pan02 tumors.
• Dual targeting of CSF-1R and IDO significantly reduced tumor burden in KPC4662.5 but not in Pan02.
• Combination therapy altered immune cell composition by decreasing PMN-MDSCs and increasing effector T cell subsets.

Interpretation:

Limitations:

• The study was conducted in murine models, which may not fully replicate human PDAC.
• The therapeutic efficacy varied between different tumor models.

Conclusion:

Combined targeting of CSF-1R and IDO alters the immune microenvironment and reduces tumor burden in fibrotic PDAC models.