{
  "abstract": "Programmed death-ligand 1 (PD-L1) undergoes continuous endocytosis and post-endocytic sorting that determine its recycling to the plasma membrane, lysosomal degradation, and exosomal secretion. Although PD-L1 internalization depends on RAB5-mediated endocytosis, whether canonical autophagy contributes to the subsequent sorting of internalized PD-L1 remains unclear. Here, we show that canonical autophagy is dispensable for the post-endocytic fate of cell-surface PD-L1. Genetic disruption of core autophagy components, including LC3B, ATG4B, ATG5, and ATG7, did not impair delivery of internalized PD-L1 to early endosomes, multivesicular bodies (MVBs), late endosomes, or extracellular vesicles. Pharmacologic inhibition of autophagosome–lysosome fusion increased PD-L1 accumulation in RAB5- and CD63-positive compartments, but this effect persisted in cells lacking LC3B, ATG5, or ATG7, further indicating that canonical autophagy is not required for PD-L1 endosomal sorting or exosomal secretion. Instead, we identify CAPZ, a CAPZα–CAPZβ heterodimer best known for actin filament capping, as a regulator of PD-L1 post-endocytic sorting. Loss of CAPZ reduced PD-L1 delivery to CD63-positive MVBs and incorporation into exosomes while increasing its accumulation in RAB11-positive recycling endosomes, resulting in elevated cell-surface PD-L1. Functionally, CAPZ-deficient tumor cells were less sensitive to peripheral blood mononuclear cell-mediated killing, consistent with increased surface PD-L1 and enhanced immune-evasive capacity. Together, these findings indicate that CAPZ-dependent endosomal maturation controls the balance between PD-L1 recycling and MVB/exosomal sorting independently of canonical autophagy, thereby influencing PD-L1 surface abundance and tumor immune evasion.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Natural and Applied Sciences, Synear Molecular Biology Lab, Jiangsu Provincial University Key (Construction) Laboratory for Smart Diagnosis and Treatment of Lung Cancer, Duke Kunshan University, Kunshan, China",
    "Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, Guangzhou, China",
    "School of Basic Medical Sciences, Shandong Second Medical University, Weifang, China",
    "City University of Hong Kong Shenzhen Research Institute, Shenzhen, China",
    "Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, China",
    "Department of Research Centre, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China",
    "College of Life Sciences, Wuhan University, Wuhan, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Peng Xu"
    },
    {
      "affs": [
        1
      ],
      "name": "Zuodong Ye"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Yanni Zhu"
    },
    {
      "affs": [
        0
      ],
      "name": "Chuen-Fuk Chan"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Yanhua Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Huiru Huang"
    },
    {
      "affs": [
        0
      ],
      "name": "Chengyi Zhu"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaoyin Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yijing Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yilin Wang"
    },
    {
      "affs": [
        3
      ],
      "name": "Naixin Lin"
    },
    {
      "affs": [
        4
      ],
      "name": "Wei Sun"
    },
    {
      "affs": [
        2
      ],
      "name": "Meiyu Peng"
    },
    {
      "affs": [
        5
      ],
      "name": "Yingying Lu"
    },
    {
      "affs": [
        0,
        2,
        6
      ],
      "name": "Jianbo Yue"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fpc0ak9f91wgc.bib",
  "cited_by": 0,
  "doi": "10.1016/j.jbc.2026.113612",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13738023/",
  "id": "fpc0ak9f91wgc",
  "issns": [
    "0021-9258",
    "1083-351X"
  ],
  "landing_url": "https://doi.org/10.1016/j.jbc.2026.113612",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "1307|Cellular transport and secretion"
    ]
  ],
  "openalex": "W7214791064",
  "pdf_url": null,
  "pmcid": "PMC13738023",
  "pmid": "42810685",
  "published": "2026-09-29",
  "publisher": "American Society for Biochemistry and Molecular Biology",
  "ris": "https://research.draconitic.com/paper/fpc0ak9f91wgc.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:23:06Z",
      "native_id": "PMC13738023",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.jbc.2026.113612"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1307|Cellular transport and secretion",
      "subfield": "cell-biology"
    }
  ],
  "title": "CAPZ regulates endosomal–exosomal trafficking of plasma membrane PD-L1 independently of canonical autophagy",
  "title_text": "CAPZ regulates endosomal–exosomal trafficking of plasma membrane PD-L1 independently of canonical autophagy",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:23:06Z",
  "url": "https://research.draconitic.com/paper/fpc0ak9f91wgc",
  "venue": "The Journal of Biological Chemistry",
  "versions": []
}