{
  "abstract": "Cancer immunotherapy has fundamentally transformed the therapeutic landscape of multiple malignancies, particularly through immune checkpoint inhibitors (ICIs) targeting the programmed cell death protein 1/programmed death ligand 1 (PD-1/PD-L1) axis and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4). However, the clinical efficacy of these agents remains limited in many patients due to primary or acquired resistance and treatment-associated immune-related adverse events (irAEs). Among emerging immunoregulatory targets, tumor necrosis factor receptor 2 (TNFR2) has attracted increasing attention owing to its preferential overexpression on highly suppressive intratumoral regulatory T cells (Tregs), which play a crucial role in immune evasion, therapeutic resistance, and unfavorable clinical outcomes across diverse malignancies. Although conventional TNFR2-targeting approaches, including monoclonal antibodies and small-molecule inhibitors, have demonstrated promising biological activity, their broader clinical translation is hindered by inadequate tumor penetration, systemic toxicity, off-target effects, and limited selectivity toward TNFR2+ immunosuppressive cell populations within the tumor microenvironment (TME). Nanoparticle-based delivery systems offer a promising platform to address these challenges by improving pharmacokinetic stability, enhancing tumor-selective accumulation, enabling TNFR2-targeting surface functionalization, and facilitating controlled payload release within the TME. In this narrative review, we summarize the molecular and immunological roles of TNFR2, examine the contribution of the TNFR2-Treg axis to tumor immune escape, and discuss current nanoparticle engineering strategies for TNFR2-directed therapy. We also evaluate emerging preclinical evidence, key translational challenges, and future perspectives for TNFR2-targeted nanomedicine in cancer immunotherapy.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia",
    "Department of Hematology, School of Medical Sciences, Universiti Sains Malaysia",
    "UPMC Hillman Cancer Center, Division of Malignant Hematology and Medical Oncology, Department of Medicine, University of Pittsburgh School of Medicine",
    "Faculty of Chemical and Energy Engineering, Universiti Technology Malaysia",
    "School of Chemical Engineering, Universiti Sains Malaysia",
    "Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, The Hashemite University",
    "Schmid College of Science and Technology, Chapman University",
    "School of Health and Biomedical Sciences, RMIT University"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Ali Akbar"
    },
    {
      "affs": [
        1
      ],
      "name": "Ali Mussa"
    },
    {
      "affs": [
        2
      ],
      "name": "Mohammad A. I. Al-Hatamleh"
    },
    {
      "affs": [
        0
      ],
      "name": "Lidawani Lambuk"
    },
    {
      "affs": [
        3
      ],
      "name": "Juhana Jaafar"
    },
    {
      "affs": [
        3
      ],
      "name": "Siti Nur Afifi Ahmad"
    },
    {
      "affs": [
        4
      ],
      "name": "JitKang Lim"
    },
    {
      "affs": [
        5
      ],
      "name": "Ma’mon M. Hatmal"
    },
    {
      "affs": [
        1
      ],
      "name": "Rosline Hassan"
    },
    {
      "affs": [
        6
      ],
      "name": "Vuk Uskoković"
    },
    {
      "affs": [
        7
      ],
      "name": "Magdalena Plebanski"
    },
    {
      "affs": [
        0
      ],
      "name": "Rohimah Mohamud"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bbwqjg6y93ss4.bib",
  "cited_by": 0,
  "doi": "10.1007/s12672-026-05486-z",
  "fulltext_url": "https://doi.org/10.1007/s12672-026-05486-z",
  "id": "bbwqjg6y93ss4",
  "issns": [
    "2730-6011"
  ],
  "landing_url": "https://doi.org/10.1007/s12672-026-05486-z",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RC254-282"
    ],
    [
      "openalex",
      "2730|Cancer Immunotherapy and Biomarkers"
    ]
  ],
  "openalex": "W7171359887",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-07-01",
  "publisher": "Springer",
  "ris": "https://research.draconitic.com/paper/bbwqjg6y93ss4.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:46:02Z",
      "native_id": "59cfebfe42b94cec97db6f49666de09b",
      "source": "doaj",
      "url": "https://doi.org/10.1007/s12672-026-05486-z"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Cancer Immunotherapy and Biomarkers",
      "subfield": "oncology"
    }
  ],
  "title": "TNFR2-targeted nanoparticles for regulatory T-cell modulation in cancer immunotherapy: a narrative review",
  "title_text": "TNFR2-targeted nanoparticles for regulatory T-cell modulation in cancer immunotherapy: a narrative review",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:46:02Z",
  "url": "https://research.draconitic.com/paper/bbwqjg6y93ss4",
  "venue": "Discover Oncology",
  "versions": []
}