{
  "abstract": "Bispecific antibodies (BsAbs) have shown marked efficacy in relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL). However, their clinical utility is constrained by cytokine release syndrome (CRS). Therefore, identification of strategies to mitigate CRS without compromising the antitumor activity of BsAbs is important. This study aimed to investigate the characteristics of CRS in BsAb therapies and identify effective intervention approaches. Analysis of serum cytokine profiles from patients receiving BsAbs revealed that IL-6, IL-8, and IL-10 levels were markedly elevated at CRS onset. Our results, together with public data, suggested that monocytes/macrophages served as the primary sources of these cytokines. In vitro experiments confirmed that the presence of macrophages substantially enhanced BsAb-induced cytokine production. In vivo macrophage depletion attenuates CRS-related cytokine release, underscoring the central role of macrophages in BsAb-induced CRS. Furthermore, in vitro experiments and in vivo humanized models have shown that bruton's tyrosine kinase (BTK) inhibitors modulate macrophage phenotype and reduce the production of IL-6, IL-8, and IL-10 without impairing the therapeutic efficacy of BsAbs. Collectively, BTK inhibitors can reduce key cytokine production in CRS by regulating the phenotype of BsAb activated macrophages, potentially lowering CRS risk and severity during BsAb therapy.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Lymphoma, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China.",
    "Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China.",
    "Department of Health Care, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital, Beijing, China.",
    "ITabMed Ltd., Shanghai, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Jiaowu Cao"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Dingyao Hu",
      "orcid": "0000-0001-7659-1431"
    },
    {
      "affs": [
        0
      ],
      "name": "Jie Lv"
    },
    {
      "affs": [
        0
      ],
      "name": "Jin Chai"
    },
    {
      "affs": [
        0
      ],
      "name": "Yue Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Jie Chen"
    },
    {
      "affs": [
        3
      ],
      "name": "Xiaoqiang Yan"
    },
    {
      "affs": [
        0
      ],
      "name": "Jun Zhu",
      "orcid": "0000-0003-3479-2547"
    },
    {
      "affs": [
        0
      ],
      "name": "Hui Yu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dwbj150dc3cap.bib",
  "cited_by": 0,
  "doi": "10.1111/cas.70575",
  "fulltext_url": "https://europepmc.org/articles/PMC13717252",
  "id": "dwbj150dc3cap",
  "issns": [
    "1347-9032",
    "1349-7006"
  ],
  "landing_url": "https://europepmc.org/article/MED/42952196",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Basic and Clinical Immunology"
    ],
    [
      "heading",
      "ORIGINAL ARTICLE"
    ],
    [
      "heading",
      "Original Article"
    ],
    [
      "openalex",
      "2734|Lymphoma Diagnosis and Treatment"
    ]
  ],
  "openalex": "W7224655290",
  "pdf_url": "https://europepmc.org/articles/PMC13717252?pdf=render",
  "pmcid": "PMC13717252",
  "pmid": "42952196",
  "published": "2026-10-28",
  "publisher": "Wiley",
  "ris": "https://research.draconitic.com/paper/dwbj150dc3cap.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:20:33Z",
      "native_id": "MED:42952196",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42952196"
    },
    {
      "first_seen": "2026-11-02T12:21:36Z",
      "native_id": "PMC13717252",
      "source": "pmc",
      "url": "https://doi.org/10.1111/cas.70575"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2734|Lymphoma Diagnosis and Treatment",
      "subfield": "general"
    }
  ],
  "title": "BTK Inhibitor Ibrutinib Reduces Bispecific Antibody-Related CRS Without Undermining the Anti-Tumor Efficacy.",
  "title_text": "BTK Inhibitor Ibrutinib Reduces Bispecific Antibody-Related CRS Without Undermining the Anti-Tumor Efficacy.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-02T12:21:36Z",
  "url": "https://research.draconitic.com/paper/dwbj150dc3cap",
  "venue": "Cancer science",
  "versions": []
}