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This research investigates how lactate influences fibroblast senescence and immune suppression in aged pancreatic cancer.

April 5, 2026

Abstract 2075: Lactate-driven cholesterol reprogramming induces fibroblast senescence and immune suppression in aged pancreatic cancer.

Key Points

This research investigates how lactate influences fibroblast senescence and immune suppression in aged pancreatic cancer.
Integrated analyses of murine and human single-cell RNA-sequencing
Multiplex immunofluorescence profiling
Targeted metabolomics and isotope tracing
Lactyl-proteomics and ATAC-seq
Cytokine profiling of secretome
Expansion of senescent cancer-associated fibroblasts (senCAFs) in aged pancreatic ductal adenocarcinoma (PDAC)
Lactate drives fibroblast senescence through upregulated MCT1 transporters
Histone lactylation (H3K18la) correlates with poor prognosis
Targeting the lactate-driven pathway improves immune response and survival in aged PDAC models

Abstract

Abstract Background: Aging profoundly remodels the pancreatic tumor microenvironment (TME), where senescent cancer-associated fibroblasts (senCAFs) accumulate and promote tumor progression. However, the metabolic cues derived from aged tumor cells that induce fibroblast senescence and mediate immune suppression remain poorly understood. Methods: Integrated analyses of murine and human single-cell RNA-sequencing datasets combined with multiplex immunofluorescence (mIF) revealed a marked enrichment of p16+ senCAFs in aged pancreatic ductal adenocarcinoma (PDAC). Targeted metabolomics and isotope tracing identified lactate as a key metabolite driving fibroblast senescence. Lactyl-proteomics, ATAC-seq, CUT Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2075.

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