Targeting the Microbiome to Enable Immunotherapeutic Efficacy in Pancreatic Carcinoma
Abstract
The PRCRP Topic Area to be addressed is "Pancreatic cancer". The PRCRP Military Relevance Focus Area is "Gaps in cancer treatment". Pancreatic ductal adenocarcinoma (PDA) is characterized by immune-tolerance and resistance to immunotherapies. The microbiome has emerged as an important factor regulating health and disease. More specifically, we and other groups have shown that the microbiome has a pathogenic role in promoting the development of PDA and in mitigating response to therapy. Our recent published work indicates that the PDA-associated microbiome is markedly expanded by more than 1000-fold compared with the normal pancreas (Pushalkar et al, Cancer Discovery 2018). Further, we found that mouse and human PDA-bearing hosts exhibit bacterial dysbiosis in the gut. Moreover, we found that the microbiome corrupts tumor immunity in PDA. Ablation of the microbiome in PDA was tumor-protective, upregulated expression of checkpoint receptors on T cells, and enabled efficacy for immunotherapy in mouse models of PDA. Based on these data, the microbiome is an attractive target in the treatment of PDA.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2021
- Accession Number
- AD1161256
Entities
People
- Xin Li
Organizations
- New York University