AI Article Synopsis
- Pancreatic ductal adenocarcinoma (PDAC) is a very dangerous type of cancer that is hard to treat, and using immunotherapy hasn't really worked well for it so far.
- Researchers tested a drug called ladarixin, which blocks certain proteins, to see if it could help treat PDAC better, especially when used with another drug called anti-PD-1.
- The results showed that ladarixin helped reduce tumors and worked well with anti-PD-1, suggesting it could be a strong option for treating this tough cancer.
Article Abstract
Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with few therapeutic options available. Despite immunotherapy has revolutionised cancer treatment, the results obtained in PDAC are still disappointing. Emerging evidence suggests that chemokines/CXCRs-axis plays a pivotal role in immune tumour microenvironment modulation, which may influence immunotherapy responsiveness. Here, we evaluated the effectiveness of CXCR1/2 inhibitor ladarixin, alone or in combination with anti-PD-1, against immunosuppression in PDAC.
Methods: A set of preclinical models was obtained by engrafting mouse PDAC-derived cells into syngeneic immune-competent mice, as well as by orthotopically transplanting patient-derived PDAC tumour into human immune-system-reconstituted (HIR) mice (HuCD34-NSG-mice). Tumour-bearing mice were randomly assigned to receive vehicles, ladarixin, anti-PD-1 or drugs combination.
Results: CXCR1/2 inhibition by ladarixin reverted in vitro tumour-mediated M2 macrophages polarisation and migration. Ladarixin as single agent reduced tumour burden in cancer-derived graft (CDG) models with high-immunogenic potential and increased the efficacy of ICI in non-immunogenic CDG-resistant models. In a HIR mouse model bearing the immunogenic subtype of human PDAC, ladarixin showed high efficacy increasing the antitumor effect of anti-PD-1.
Conclusion: Ladarixin in combination with anti-PD-1 might represent an extremely effective approach for the treatment of immunotherapy refractory PDAC, allowing pro-tumoral to immune-permissive microenvironment conversion.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9902528 | PMC |
| http://dx.doi.org/10.1038/s41416-022-02028-6 | DOI Listing |
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