In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 79, No. 24_Supplement ( 2019-12-15), p. A19-A19
Abstract:
Pancreatic ductal adenocarcinoma (PDA) is the third most common cause of cancer death in the US with a 9% 5-year survival rate. PDA is characterized by a robust stromal reaction, a large portion of which is composed of infiltrating immune cells and supported by fibroblasts. This fibroinflammatory response promotes both the initiation and progression of PDA. Key to this progression is the crosstalk between the tumor epithelium and immune compartment. Metaplastic tuft cells (MTCs) are a subset of the neoplastic epithelium derived by the transdifferentiation of acinar cells. Tuft cells have been characterized to have a “sense-and-respond” role in luminal surfaces throughout the body, using the taste chemosensory system to promote an inflammatory response in infected and damaged tissues. Among the pancreatic epithelium, MTCs uniquely express components of the gustation sensory system including taste receptors, TRPM5 and αGustducin, as well as an array of inflammatory cytokines, suggesting they are capable of promoting an immune response to extracellular challenges. To explore this hypothesis, we ablated αGustducin, a key protein in the chemosensory cascade, in a model of pancreatitis-associated tumorigenesis. We found that neoplasia in the GNAT3-/-; KrasG12D; PTF1aCreERT mice initiates and progresses more rapidly, a difference associated with alteration in immune cell subtypes. To further quantitate changes in the immune response, we performed mass cytometry (CyTOF), as a way to explore changes in cell number and type, and single-cell sequencing, to more deeply probe the unique gene signatures of cells within the tumor stroma. These large-scale analyses suggest substantial changes in the number of T-cell and myeloid cell populations, as well as alterations of fibroblasts and myeloid cell polarity. We conclude that MTCs use chemosensory signaling to promote the formation of a tumor-suppressive microenvironment. Citation Format: Megan T. Hoffman, Stephanie The, Daniel J. Salas-Escabillas, Kathleen E. DelGiorno, Filip Bednar, Robert F. Margolskee, Arvind Rao, Howard C. Crawford. The role of metaplastic tuft cell chemosensory signaling in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr A19.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.PANCA19-A19
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2019
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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