{
  "abstract": "Pulsed low-dose-rate radiotherapy (PLDR) is a promising reirradiation strategy for refractory solid tumors because of its potential to reduce normal tissue toxicity; however, its immunomodulatory mechanisms remain poorly understood. In this study, we retrospectively analyzed clinical outcomes and treatment-related adverse events in 16 patients with refractory solid tumors treated with PLDR. Using MC38 tumor-bearing mice, we compared PLDR and conventional radiotherapy (cRT) under biologically equivalent dose conditions and performed single-cell RNA sequencing to characterize treatment-associated remodeling of the tumor immune microenvironment (TIM). Multiplex immunofluorescence staining and spatial analysis were further conducted in an independent cohort of 114 patients with rectal cancer to evaluate the clinical relevance of identified immune features. PLDR achieved comparable local tumor control to cRT while reducing treatment-related toxicity and improving overall survival (OS) in mouse models. In the combination-treatment setting, single-cell analyses showed that PLDR + immunotherapy with an anti-PD-1 antibody combined with the targeted agent anlotinib (ITT), compared with cRT + ITT, was associated with enrichment of Gzmk⁺ CD8⁺ T cells, reduced Spp1⁺ tumor-associated macrophages (TAMs) abundance, and altered cell–cell communication between these populations. In our independent rectal cancer cohort, the spatial distance between SPP1⁺ TAMs and GZMK⁺ CD8⁺ T cells was independently associated with OS. These findings suggest that the interaction between SPP1⁺ TAMs and GZMK⁺ CD8⁺ T cells may be closely associated with PLDR-related TIM remodeling and may also serve as a potential prognostic biomarker in rectal cancer.\n\nSupplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s10565-026-10324-7.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Radiation Oncology, Fujian Medical University Union Hospital, Fuzhou, China",
    "Fujian Key Laboratory of Intelligent Imaging and Precision Radiotherapy for Tumors (Fujian Medical University), Fuzhou, Fujian China",
    "Clinical Research Center for Radiology and Radiotherapy of Fujian Province (Digestive, Hematological and Breast Malignancies), Fuzhou, Fujian China",
    "Department of Radiation Oncology, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian China",
    "Department of Oncology, Jinjiang Hospital of Traditional Chinese Medicine, Jinjiang, Fujian China",
    "Department of Oncology, Zhangzhou Second Hospital, Zhangzhou, Fujian China",
    "Department of Radiation Oncology, Putian No.95 Hospital, Putian, Fujian China",
    "Department of Radiation Oncology, Quanzhou Binhai Hospital, Quanzhou, Fujian China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Zihan Zhou"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Yafang Hong"
    },
    {
      "affs": [
        0
      ],
      "name": "Jianhang You"
    },
    {
      "affs": [
        0
      ],
      "name": "Kaiqian Que"
    },
    {
      "affs": [
        4
      ],
      "name": "Yiming Lan"
    },
    {
      "affs": [
        5
      ],
      "name": "Yineng Lin"
    },
    {
      "affs": [
        6
      ],
      "name": "Junying Peng"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Zhenyu Lin"
    },
    {
      "affs": [
        0
      ],
      "name": "Lanshan Li"
    },
    {
      "affs": [
        7
      ],
      "name": "Lu Han"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Benhua Xu",
      "orcid": "0009-0002-3577-7672"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bqq7gbqtxj3pg.bib",
  "cited_by": 0,
  "doi": "10.1007/s10565-026-10324-7",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13736382/",
  "id": "bqq7gbqtxj3pg",
  "issns": [
    "0742-2091",
    "1573-6822"
  ],
  "landing_url": "https://doi.org/10.1007/s10565-026-10324-7",
  "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"
    ],
    [
      "openalex",
      "2730|Cancer Immunotherapy and Biomarkers"
    ]
  ],
  "openalex": "W7225230017",
  "pdf_url": null,
  "pmcid": "PMC13736382",
  "pmid": "42982946",
  "published": "2026-11-04",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/bqq7gbqtxj3pg.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:21:50Z",
      "native_id": "PMC13736382",
      "source": "pmc",
      "url": "https://doi.org/10.1007/s10565-026-10324-7"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Cancer Immunotherapy and Biomarkers",
      "subfield": "oncology"
    }
  ],
  "title": "Pulsed Low-dose-rate Radiotherapy Remodels the Tumor Immune Microenvironment and is Associated With Crosstalk Between SPP1⁺ tumor-associated macrophages and GZMK⁺ CD8⁺ T cells",
  "title_text": "Pulsed Low-dose-rate Radiotherapy Remodels the Tumor Immune Microenvironment and is Associated With Crosstalk Between SPP1⁺ tumor-associated macrophages and GZMK⁺ CD8⁺ T cells",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:21:50Z",
  "url": "https://research.draconitic.com/paper/bqq7gbqtxj3pg",
  "venue": "Cell Biology and Toxicology",
  "versions": []
}