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anti- pd-1/pd-l1 immunotherapy article download pdf crispr/cas9 gene editing stimulated alongside anti-cd3 rna-induced silencing complex cancer-related signaling pathways trna-derived small rnas prevent anti-pd-1-treated cd8 membrane-type matrix metalloproteases hrp-conjugated secondary antibodies pd-l1/pd-1 blockade pd-1/pd-l1 inhibitors trna-derived small rna enzyme-linked immunosorbent assay scrna-seq results revealed pd-1/pd-l1 blockers single-cell rna sequencing secreting caf-specific proteins anti-cancer immune response pi3k-akt signaling pathway caf-based risk signature xiaorong mu designed fluorescently labeled kyse30 bone marrow-derived fibroblasts full access neurotrophin signaling pathways treatment search search disability-adjusted life-years mmp14-cafs cell subsets privacy choices/manage cookies pd-1 monoclonal antibody scrna-seq analysis demonstrated type iv collagen mmp14+ cafs-derived exosomes mapk signaling pathways protein-binding regulation modes pd-1 antibody therapy combining pd-1 immunotherapy fixed alongside paraformaldehyde treated alongside annexin related subjects significant cell type hippo signaling pathways anti-pd-1-treated including single-cell distinctly expressed tsrna cell receptor pathway crispr/cas cell infiltration levels tumor cell killing

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         headline:The mechanism of MMP14-positive tumor-associated fibroblast subsets in inhibiting PD-1 immunotherapy for esophageal cancer through exosomal tsRNA-10522
         description:Esophageal cancer (EC) continues to pose a significant health risk. Cancer-associated fibroblasts (CAFs), an essential part of the tumor microenvironment (TME), are viewed as potential therapeutic targets. However, their role in tumor mechanisms specific to esophageal cancer remains to be elucidated. This study identified MMP14+ CAFs and MMP14- CAFs using immunofluorescence staining. The cytotoxic activity of CD8 T cells was assessed via western blot and ELISA. Using a transwell test, the migratory potential of MMP14+ CAFs was evaluated. Using flow cytometry, apoptosis was found in the esophageal squamous cell carcinoma cell line KYSE30. To determine the important tsRNAs released by MMP14+ CAFs, tsRNA-seq was used. Two subgroups of EC receiving PD-1 immunotherapy were identified by our research: MMP14+ CAFs and MMP14- CAFs. MMP14+ CAFs showed improved migratory capacity and released more inflammatory factors linked to cancer. Through exosomes, these CAFs may prevent anti-PD-1-treated CD8 T cells from being cytotoxic. Furthermore, exosomal tsRNA from MMP14+ CAFs primarily targeted signaling pathways connected with cancer. Notably, it was discovered that tsRNA-10522 plays a critical role within inhibiting CD8 T cell tumor cell death. The tumor cell killing of CD8 T cells by exosomal tsRNA-10522 is inhibited by a subgroup of cells called MMP14+ CAFs inside the EC microenvironment during PD-1 immunotherapy. This reduces the effectiveness of PD-1 immunotherapy for EC. Our findings demonstrate the inhibitory function of MMP14+ CAFs within EC receiving PD-1 immunotherapy, raising the prospect that MMP14+ CAFs might serve as predictive indicators in EC receiving PD-1 immunotherapy.
         datePublished:2024-10-08T00:00:00Z
         dateModified:2024-10-08T00:00:00Z
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            Esophageal cancer
            PD-1 immunotherapy
            MMP14+ Cancer-associated fibroblasts
            Exosome
            TsRNA-10522
            Cell Biology
            Plant Genetics and Genomics
            Microbial Genetics and Genomics
            Biochemistry
            general
            Bioinformatics
            Animal Genetics and Genomics
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      headline:The mechanism of MMP14-positive tumor-associated fibroblast subsets in inhibiting PD-1 immunotherapy for esophageal cancer through exosomal tsRNA-10522
      description:Esophageal cancer (EC) continues to pose a significant health risk. Cancer-associated fibroblasts (CAFs), an essential part of the tumor microenvironment (TME), are viewed as potential therapeutic targets. However, their role in tumor mechanisms specific to esophageal cancer remains to be elucidated. This study identified MMP14+ CAFs and MMP14- CAFs using immunofluorescence staining. The cytotoxic activity of CD8 T cells was assessed via western blot and ELISA. Using a transwell test, the migratory potential of MMP14+ CAFs was evaluated. Using flow cytometry, apoptosis was found in the esophageal squamous cell carcinoma cell line KYSE30. To determine the important tsRNAs released by MMP14+ CAFs, tsRNA-seq was used. Two subgroups of EC receiving PD-1 immunotherapy were identified by our research: MMP14+ CAFs and MMP14- CAFs. MMP14+ CAFs showed improved migratory capacity and released more inflammatory factors linked to cancer. Through exosomes, these CAFs may prevent anti-PD-1-treated CD8 T cells from being cytotoxic. Furthermore, exosomal tsRNA from MMP14+ CAFs primarily targeted signaling pathways connected with cancer. Notably, it was discovered that tsRNA-10522 plays a critical role within inhibiting CD8 T cell tumor cell death. The tumor cell killing of CD8 T cells by exosomal tsRNA-10522 is inhibited by a subgroup of cells called MMP14+ CAFs inside the EC microenvironment during PD-1 immunotherapy. This reduces the effectiveness of PD-1 immunotherapy for EC. Our findings demonstrate the inhibitory function of MMP14+ CAFs within EC receiving PD-1 immunotherapy, raising the prospect that MMP14+ CAFs might serve as predictive indicators in EC receiving PD-1 immunotherapy.
      datePublished:2024-10-08T00:00:00Z
      dateModified:2024-10-08T00:00:00Z
      pageStart:1
      pageEnd:15
      license:http://creativecommons.org/licenses/by-nc-nd/4.0/
      sameAs:https://doi.org/10.1007/s10142-024-01447-3
      keywords:
         Esophageal cancer
         PD-1 immunotherapy
         MMP14+ Cancer-associated fibroblasts
         Exosome
         TsRNA-10522
         Cell Biology
         Plant Genetics and Genomics
         Microbial Genetics and Genomics
         Biochemistry
         general
         Bioinformatics
         Animal Genetics and Genomics
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               type:PostalAddress
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            address:
               name:Basic Medical College, Air Force Medical University, Xi’an, China
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               type:PostalAddress
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      name:Xiaorong Mu
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      name:Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi’an, China
      name:Basic Medical College, Air Force Medical University, Xi’an, China
      name:College of Life Sciences, Northwest University, Xi’an, China
      name:Basic Medical College, Air Force Medical University, Xi’an, China
      name:Basic Medical College, Air Force Medical University, Xi’an, China
      name:Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi’an, China
      name:Department of Pathology, Department of Pharmacy, Tangdu Hospital, Air Force Medical University, Xi’an, China
      name:Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi’an, China

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