{
  "abstract": "Background: T-cell function is regulated by immunometabolism, and lysosomes are signaling hubs. CD68 (LAMP4), traditionally regarded as a monocyte/macrophage marker, has been largely neglected in T cell biology. We aimed to assess the link between CD68 expression in T cells and anti-PD-1 response in lung cancer, and its potential as an early dynamic biomarker in peripheral blood CD8 ⁺ T cells.\n\nMethods: We analyzed transcriptomic (GSE126044, GSE135222, GSE166449) and single-cell (GSE207422) data from anti-PD-1-treated lung cancer cohorts to identify lysosome related pathways and key genes, validated with peripheral blood CD8 ⁺ T cell data (GSE111414). Prospectively, we enrolled lung cancer patients receiving anti-PD-1 therapy, collecting peripheral blood at baseline and week 3. Flow cytometry measured CD68 in CD8 ⁺ T cells and subsets, assessing association with response, progression-free survival (PFS), and functional markers (granzyme B, perforin, Ki-67, CD69, IFN-γ, IL-1β).\n\nResults: Responders showed enrichment of lysosome pathways and upregulation of 8 lysosome related genes including CD68, positively correlated with monocyte and T cell infiltration. Single-cell data linked CD68 expression in T cell to favorable response. After one cycle, the proportion of CD8 ⁺ CD68 ⁺ T cells was lower in non-responders ( P<0.05 ), with AUC 0.803 ( P=0.044 ) and cutoff 1.015%, stratifying PFS ( P=0.0225 ). CD68 was highest in naïve T cells at baseline, but decreased across subsets after treatment in non-responders (all P<0.01 ). Functionally, compared with CD8 ⁺ CD68 ⁻ T cells, CD8 ⁺ CD68 ⁺ T cells exhibited lower expression of granzyme B and perforin but higher expression of Ki-67, CD69, IFN-γ, and IL-1β (all P<0.001 ), suggesting a CD8 ⁺ T cell state characterized by lower cytotoxicity and enhanced proliferative and cytokine producing capacities, accompanied by a tissue residency associated phenotype.\n\nConclusion: CD8 ⁺ CD68 ⁺ T cells exhibit lower cytotoxicity but greater proliferative and cytokine producing capacities, together with a tissue residency associated phenotype, suggesting a precursor-like state. Low CD68 expression in tumor-infiltrating T cells and the post-treatment reduction of CD68 expression in peripheral blood CD8 ⁺ T cells are associated with resistance to anti-PD-1 therapy in lung cancer. These findings suggest that CD8 ⁺ CD68 ⁺ T cells may serve as a potential early dynamic immune biomarker for monitoring and assessing response to anti-PD-1 therapy in lung cancer.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Laboratory Medicine, Infectious Diseases and Pathogen Biology Center, The First Hospital of Jilin University"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Ying Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Jing Huang"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhengyi Sun"
    },
    {
      "affs": [
        0
      ],
      "name": "Yumei Pei"
    },
    {
      "affs": [
        0
      ],
      "name": "Jiancheng Xu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/e16yd6zax43n8.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1995008",
  "fulltext_url": "https://europepmc.org/articles/PMC13710226",
  "id": "e16yd6zax43n8",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1995008/full",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "2730|Cancer Immunotherapy and Biomarkers"
    ]
  ],
  "openalex": "W7221602079",
  "pdf_url": "https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1995008/pdf",
  "pmcid": "PMC13710226",
  "pmid": "42947988",
  "published": "2026-10-13",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/e16yd6zax43n8.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:15Z",
      "native_id": "10.3389/fimmu.2026.1995008",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1995008/full"
    },
    {
      "first_seen": "2026-10-31T00:20:34Z",
      "native_id": "MED:42947988",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42947988"
    },
    {
      "first_seen": "2026-10-31T12:21:14Z",
      "native_id": "PMC13710226",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fimmu.2026.1995008"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Cancer Immunotherapy and Biomarkers",
      "subfield": "oncology"
    }
  ],
  "title": "A CD68-expressing tissue-homing subset in peripheral CD8+ T cells predicts response to anti-PD-1 therapy in lung cancer",
  "title_text": "A CD68-expressing tissue-homing subset in peripheral CD8+ T cells predicts response to anti-PD-1 therapy in lung cancer",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:21:14Z",
  "url": "https://research.draconitic.com/paper/e16yd6zax43n8",
  "venue": "Frontiers in Immunology",
  "versions": []
}