Pancreatic cancer cells overexpressing interleukin 6 induce T-cell-mediated tumor clearance and durable anti-tumor immune response.

Autor:	Arneson-Wissink PC; Department of Radiation Medicine, Oregon Health & Science University, Portland, OR, 97239, USA., Bartlett AQ; Division of Surgical Oncology, Department of Surgery, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, 97239, USA., Mendez H; Department of Radiation Medicine, Oregon Health & Science University, Portland, OR, 97239, USA., Zhu X; Department of Radiation Medicine, Oregon Health & Science University, Portland, OR, 97239, USA., Dickie J; Department of Radiation Medicine, Oregon Health & Science University, Portland, OR, 97239, USA., McWhorter M; Division of Surgical Oncology, Department of Surgery, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, 97239, USA., Levasseur PR; Department of Radiation Medicine, Oregon Health & Science University, Portland, OR, 97239, USA., Diba P; Department of Radiation Medicine, Oregon Health & Science University, Portland, OR, 97239, USA., Byrne KT; Department of Cell, Development, and Cancer Biology, Oregon Health & Science University,Portland, OR, 97239, USA.; Brenden Colson Center for Pancreatic Care, Oregon Health & Science University, Portland,OR, 97239, USA., Scott GD; Department of Pathology, Oregon Health & Science University, Portland, OR, 97239, USA., Eil R; Division of Surgical Oncology, Department of Surgery, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, 97239, USA., Grossberg AJ; Department of Radiation Medicine, Oregon Health & Science University, Portland, OR, 97239, USA.; Brenden Colson Center for Pancreatic Care, Oregon Health & Science University, Portland,OR, 97239, USA.; Cancer Early Detection Advanced Research Center, Oregon Health & Science University,Portland, OR, 97201, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Sep 27. Date of Electronic Publication: 2024 Sep 27.
DOI:	10.1101/2024.09.26.615308
Abstrakt:	Tumor immune resistance is recognized as a contributor to low survivorship in pancreatic ductal adenocarcinoma (PDAC). We developed a novel murine model of spontaneous PDAC clearance, generated by overexpressing interleukin-6 (IL-6) in orthotopically implanted PDAC cancer cells (OT-PDAC IL6 ). Circulating IL-6 was 100-fold higher in OT-PDAC IL6 than in OT-PDAC parental mice. OT-PDAC IL6 tumors were present at 5 days post-implantation, and undetectable by 10 days post implantation. Flow cytometry revealed increased T cells and NK cells, and decreased T regulatory cells in OT-PDAC IL6 as compared to OT-PDAC parental tumors. Increased lymphoid aggregates were apparent by histological assessment and may account for elevated T cell content. Antibody-based depletion of CD4 + and CD8 + T cells prevented tumor clearance and significantly reduced survival of OT-PDAC IL6 mice. The anti-tumor immune response to OT-PDAC IL6 rendered mice immune to re-challenge with OT-PDAC parental tumors. In high concentrations, IL-6 acts in opposition to previously described pro-tumorigenic effects by enhancing the T cell-mediated anti-tumor response to PDAC. Competing Interests: Conflict of interest: RE is a paid consultant and conducts ongoing research for Lyell Immunopharma. KTB receives consultation feed from Guidepoint Global and royalties from theUniversity of Pennsylvania for licensed research cell lines. The other authors declare no conflicts.
Databáze:	MEDLINE
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