Accession Number:

AD1161256

Title:

Targeting the Microbiome to Enable Immunotherapeutic Efficacy in Pancreatic Carcinoma

Descriptive Note:

[Technical Report, Annual Report]

Corporate Author:

NEW YORK UNIV NY

Personal Author(s):

Report Date:

2021-10-01

Pagination or Media Count:

16

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.

Subject Categories:

  • Medicine and Medical Research

Distribution Statement:

[A, Approved For Public Release]