ArticleJournal for immunotherapy of cancer2022
Enhanced antigen cross-presentation in human colorectal cancer-associated fibroblasts through upregulation of the lysosomal protease cathepsin S.
Article in Journal for immunotherapy of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 38 citations in OpenAlex.
- Review
- From inflammation to malignancy: the dynamic evolution of cancer-associated fibroblasts in IBD-CRC.Neoplasia (New York, N.Y.) · 2026Review
- Single-cell profiling reveals a novel CAF subpopulation linking stromal heterogeneity to immune suppression in breast cancer subtypes.Journal of translational medicine · 2026Article
- Cancer-associated fibroblasts and tertiary lymphoid structure orchestrate the spatial architecture of tumor immunity.Journal of hematology & oncology · 2026Review
- Targeting fibroblast TXNDC5 resolves tumor desmoplasia and PD-1 resistance in colorectal cancer with mesenchymal traits.Nature communications · 2026Article
- Article
- Cross-Priming and Cross-Tolerance After Intramuscular mRNA Vaccination for Viral Infections: Feasibility and Implications.Life (Basel, Switzerland) · 2025Review
- Cathepsins: Emerging targets in the tumor ecosystem to overcome cancers.Seminars in cancer biology · 2025Review
- Stromal Cell Subsets Show Model-Dependent Changes in Experimental Colitis and Affect Epithelial Tissue Repair and Immune Cell Activation.Inflammatory bowel diseases · 2025Article
- Antigen-presenting fibroblasts: emerging players in immune modulation and therapeutic targets.Theranostics · 2025Review
- FOS-driven inflammatory CAFs promote colorectal cancer liver metastasis via the SFRP1-FGFR2-HIF1 axis.Theranostics · 2025Article
- The multifaceted roles of cathepsins in immune and inflammatory responses: implications for cancer therapy, autoimmune diseases, and infectious diseases.Biomarker research · 2024Review
- Crosstalk between cancer-associated fibroblasts and non-neuroendocrine tumor cells in small cell lung cancer involves in glycolysis and antigen-presenting features.Molecular medicine (Cambridge, Mass.) · 2024Article
- Cancer-associated fibroblast subtypes modulate the tumor-immune microenvironment and are associated with skin cancer malignancy.Nature communications · 2024Article
- Drug resistance and tumor immune microenvironment: An overview of current understandings (Review).International journal of oncology · 2024Review
- Reduced expression of cathepsin F predicts poor prognosis in patients with clear cell renal cell carcinoma.Scientific reports · 2024Article
- A pan-cancer single-cell transcriptional analysis of antigen-presenting cancer-associated fibroblasts in the tumor microenvironment.Frontiers in immunology · 2024Article
- Fibroblasts in Orchestrating Colorectal Tumorigenesis and Progression.Cellular and molecular gastroenterology and hepatology · 2024Review
- The Tango between Cancer-Associated Fibroblasts (CAFs) and Immune Cells in Affecting Immunotherapy Efficacy in Pancreatic Cancer.International journal of molecular sciences · 2023Review
- The advent of immune stimulating CAFs in cancer.Nature reviews. Cancer · 2023Review
Corrections and comments
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Authors and funding
18 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCross-presentation of exogenous antigens in HLA-class I molecules by professional antigen presenting cells (APCs) is crucial for CD8+ T cell function. Recent murine studies show that several non-professional APCs, including cancer-associated fibroblasts (CAFs) also possess this capacity. Whether human CAFs are able to cross-present exogenous antigen, which molecular pathways are involved in this process and how this ultimately affects tumor-specific CD8+ T cell function is unknown.
methodsIn this study, we investigated the ability of human colorectal cancer (CRC)-derived CAFs to cross-present neoantigen-derived synthetic long peptides (SLPs), corresponding to tumor-derived mutant peptides, and how this affects tumor-specific T-cell function. Processing of the SLP was studied by targeting components of the cross-presentation machinery through CRISPR/Cas9 and siRNA-mediated genetic ablation to identify the key molecules involved in fibroblast-mediated cross-presentation. Multispectral flow cytometry and killing assays were performed to study the effect of fibroblast cross-presentation on T cell function.
resultsHere, we show that human CRC-derived CAFs display an enhanced capacity to cross-present neoantigen-derived SLPs when compared with normal colonic fibroblasts. Cross-presentation of antigens by fibroblasts involved the lysosomal protease cathepsin S. Cathepsin S expression by CAFs was detected in situ in human CRC tissue, was upregulated in ex vivo cultured CRC-derived CAFs and showed increased expression in normal fibroblasts after exposure to CRC-conditioned medium. Cognate interaction between CD8+ T cells and cross-presenting CAFs suppressed T cell function, reflected by decreased cytotoxicity, reduced activation (CD137) and increased exhaustion (TIM3, LAG3 and CD39) marker expression.
conclusionThese data indicate that CAFs may directly suppress tumor-specific T cell function in an antigen-dependent fashion in human CRC.
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