SCIENCE

Barriers to Treatment in the Pancreas

Pancreatic ductal adenocarcinomas (PDAC) have a highly fibrotic tumor microenvironment (TME) and high immunosuppressive cell infiltration, limiting the efficacy of immunotherapy.1,2

Scientific illustration of a tumor in the pancreas and a small delivery device approaching the tumor via the venous system

Intratumoral Pressure (ITP) in the Pancreas

The PDAC TME induces angiogenesis through vascular endothelial growth factor (VEGF), resulting in disorganized tumor vasculature, hypoxia and high ITP. These factors profoundly impact immuno-oncology drug delivery and efficacy.3

Systemic drug delivery distributes the majority of a drug outside of the pancreas and fails to create an adequate pressure gradient to overcome intratumoral pressure.1

Overcoming Intratumoral Pressure

Our proprietary technology has been shown to overcome ITP and reopen blood vessels.

Scientific illustration of a pancreas with a pancreatic ductal adenocarcinoma

Intratumoral pressure in the pancreas

The PDAC TME induces angiogenesis through vascular endothelial growth factor (VEGF), resulting in disorganized tumor vasculature, hypoxia and high intratumoral pressure (ITP), profoundly impacting immuno-oncology drug delivery and efficacy.3

Systemic drug delivery distributes the majority of a drug outside of the pancreas and fails to create an adequate pressure gradient to overcome intratumoral pressure.1

Overcoming Intratumoral Pressure

Our proprietary technology has been shown to overcome ITP and reopen blood vessels.

Immunosuppression in Pancreatic Tumors

The PDAC TME is primarily made up of pancreatic stellate cells (PSC), extracellular matrix and immunosuppressive cellular populations.1 At baseline, the PDAC TME contains few active T cells, the absence of which is further exacerbated by tumor-associated macrophages (TAM) and myeloid-derived suppressor cells (MDSCs).4

Upregulation of TAMs drives the secretion of immunosuppressive cytokines, recruitment of regulatory T cells (Treg), interference of effector and cytotoxic T cells, and additional upregulation of PSCs.5–7

The presence of myeloid-derived suppressor cells (MDSC) further contributes to the immunosuppressive PDAC TME.1,2

Scientific illustration of myeloid-derived suppressor cells.
MDSCs
Scientific illustration of T-cells and B-cells
T Cells & B Cells

MDSCs in Pancreatic Tumors Limit Impact Of Immunotherapy

In addition to Treg, suppressive myeloid cells are recruited to the PDAC TME.1,2 MDSCs are critical drivers of poor responses in the pancreas due to further suppression of effector T-cell function using reactive oxygen species, production of adenosine and inducing Treg development through secretion of IFNγ and IL10.8

Overcoming Immunosuppression
Immunomodulatory drugs have the potential to reactivate the immune system.

Improving Drug Delivery and Efficacy in the Pancreas

At TriSalus, we believe that a therapeutic approach that simultaneously reduces immunosuppressive populations and improves therapeutic delivery to tumor tissue holds great promise for patients with few good options.

PLATFORM

CITATIONS

  1. Feig C, et al. Clin Cancer Res. 2012;18(16):4266-4276.
  2. Looi CK, et al. J Exp Clin Cancer Res. 2019;38(1):162.
  3. Tsuzuki Y, et al. Lab Invest. 2001;81(10):1439-1451.
  4. Ho WJ, et al. Nat Rev Clin Oncol. 2020;17(9):527-540.
  5. Noy R, et al. Immunity. 2014;41(1):49-61.
  6. Gomez-Chou SB, et al. Cancer Res. 2017;77(10):2647-2660.
  7. Ren B, et al. Mol Cancer. 2018;17:108.
  8. Groth C, et al. Br J Cancer. 2019;120(1):16-25.

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