Key Features
Enhance your research with our curated data sets and powerful platform features. Pluto Bio makes it simple to find and use the data you need.
Learn MoreBackground: Treatment with single-agent decitabine (5aza-dC; DAC), a well-tolerated DNA hypomethylating drug, in a mouse model of pancreatic ductal adenocarcinoma (PDAC), KPC-Brca1, extended the survival of the animals and upregulated immune-related pathways. Here we extend these findings to combination therapy, using DAC followed by the immune checkpoint inhibitor anti-PD-1H in the original more widely utilized KPC (Pdx-Cre Kras/p53) model. Methods: We treated tumor-bearing KPC mice with DAC, and with anti-PD-1H, separately and in combination, and assessed tumor growth, mouse survival, immune cell infiltration of the tumors, and gene expression, compared to historical and mock-treated control mice. Results: Treatment with single-agent DAC led to increased Cd8+ tumor-infiltrating T cells (TILs), increased tumor necrosis, and slower tumor growth. RNA-seq analysis revealed increased expression of a group of myeloid-lineage markers, including Chi3l3 (Ym1), which proved to reflect recruitment or expansion of a unique population of Chi3l3/Arginase-1 double-positive M2-polarized tumor-infiltrating myeloid cells. Anti-PD-1H alone had only modest effects on tumor growth and number of Cd8+ TILs. However, PD-1H-expressing TILs were significantly increased by single agent DAC, and DAC treatment followed by anti-PD-1H produced the strongest increase in Cd8+ TILS, inhibition of tumor growth, and prolongation of survival. Conclusions: Treatment with DAC alone, and DAC plus anti-PD-1H, inhibits PDAC tumor growth in the KPC model and produces changes in tumor-infiltrating lymphoid and myeloid cell populations, with an additive therapeutic benefit from combining the two agents. Since the influx of M2-polarized macrophages induced by DAC is predicted to antagonize the anti-tumor effects, future work should investigate eliminating or reprogramming these cells. SOURCE: Tamas Gonda (tg2214@columbia.edu) - Columbia University
View on GEOView in PlutoEnhance your research with our curated data sets and powerful platform features. Pluto Bio makes it simple to find and use the data you need.
Learn MoreUse Pluto's intuitive interface to analyze and visualize data for this experiment. Pluto's platform is equipped with an API & SDKs, making it easy to integrate into your internal bioinformatics processes.
Read about post-pipeline analysisView quality control data and experiment metadata for this experiment.
Request imports from GEO or TCGA directly within Pluto Bio.
Chat with our Scientific Insights team