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Table 3 Intervention strategy with or without other checkpoint inhibitor

From: Therapeutic challenges and current immunomodulatory strategies in targeting the immunosuppressive pancreatic tumor microenvironment

Class Intervention Strategy Results Reference(s)
CSF1R IMC-CS4 (CSF1R mAb) + anti-PD-1 or anti-CTLA-4 ↑CTL infiltration
↓ Treg infiltration
↑ Antitumor immunity
↓ Tumor growth
[52, 53]
PLX-3397 (anti-CSF1R) + durvalumab (anti-PD-L1 Ab) Ongoing Phase I study in advanced pancreatic and colorectal cancers NCT02777710
JAK/STAT Ruxolitinib (JAK/STAT inhibitor) ↓ Tumor growth
↓ PD-L1 expression
↑ CD8+ T cells
Ruxolitinib + capecitabine ↑ survival in metastatic pancreatic cancer who failed to response gemcitabine [58]
BTK Ibrutinib (BTK inhibitor) ↓ Infiltration of mast cells
↓ Stromal fibrosis
↓ Tumor progression
↓ IL-2 inducible T-cell kinase
[62, 63]
Ibrutinib + gemcitabine + nab-paclitaxel Ongoing Phase I/II study in metastatic pancreatic cancer NCT02562898
Ibrutinib + gemcitabine + nab-paclitaxel Ongoing Phase II/III study in metastatic pancreatic cancer NCT02436668
Radio-therapy (RT) RT (12 Gy or 5 × 3 Gy) + PD-L1 blocker ↓ Tumor growth
↓ Treg/MDSC infiltration
[64, 65]
RT + anti-CTLA-4 mAb / anti-PD-L1 Ongoing phase Ib in unresctable, non-metastatic pancreatic cancer NCT02868632
RT + ipilimumab (anti-CTLA-4 mAb) / nivolumab (anti-PD-L1) Ongoing phase II in metastatic pancreatic cancer NCT02866383
RT + tremelimumab / MEDI4736 Ongoing phase I/II in unresectable metastatic pancreatic cancer NCT02311361