Biology subjects

Garcin, P.

Publications and source records attributed to Garcin, P..

2 recordsLinked to original sources

bioRxiv2023

Minute virus of mice is oncolytic for pancreatic cancer cells with mesenchymal phenotype

Pancreatic cancer will soon become the second cause of death by cancer in Western countries. The main barrier to increase the survival of patients with this disease requires the development of novel and efficient therapeutic strategies, that better consider tumor biology. Oncolytic viruses are quickly moving toward the forefront of medicines for the management of cancer. Among them, the fibrotropic minute virus of mice prototype (MVMp) preferentially infects migrating and undifferentiated cells, that highly resemble poorly differentiated, basal-like, pancreatic tumors showing the worst clinical outcome. Thus, we hypothesized that MVMp may specifically target the most aggressive subtype of pancreatic cancer cells. We report here that MVMp specifically infects, replicates in and kills pancreatic cancer cells from murine and human origin with a mesenchymal, basal-like profile, while sparing cancer cells with an epithelial phenotype. In vivo, MVMp shows oncolytic activity in experimental tumors with mesenchymal phenotype only, and shows increased antitumoral efficacy in immune competent models. Collectively, we demonstrate herein for the first time that MVMp is specific and oncolytic for pancreatic tumors with mesenchymal, basal-like profile, paving the way for precision medicine opportunities for the management of the most aggressive and lethal form of this disease.

cancer biology↗

bioRxiv2020

The antitumoral activity of TLR7 ligands is corrupted by the microenvironment of pancreatic tumors

Toll like receptors are key players in the innate immune system. Recent studies have suggested that they may impact the growth of pancreatic cancer, a disease with no cure. Among them, Toll like receptor-7 shows promise for therapy but may also promote tumor growth. Thus, we aimed to better understand the mechanism of action of Toll like receptor-7 ligands in pancreatic cancer, to open the door for clinical applications. In vitro, Toll like receptor-7 ligands strongly inhibit the proliferation and induce cell death by apoptosis of pancreatic cancer cells. In vivo, while Toll like receptor-7 agonists significantly delay the growth of aggressive tumors engrafted in immunodeficient mice, they instead surprisingly promote tumor growth and accelerate animal death in immunocompetent models. Molecular investigations revealed that Toll like receptor-7 agonists strongly increase the number of tumor-promoting macrophages to drive pancreatic tumorigenesis in immunocompetent mice. This is in stark contrast with Toll like receptor-7 ligands great potential to inhibit pancreatic cancer cell proliferation in vitro and tumor growth in vivo in immunosuppressed models. Collectively, our findings shine a light on the duality of action of Toll like receptor-7 agonists in experimental cancer models, and calls into question their use for pancreatic cancer therapy.

cancer biology↗