{
  "abstract": "Adoptive antitumor immunity ultimately fails because metabolically hostile tumor microenvironments (TME) drive T cells into a dysfunctional exhausted state that current checkpoint blockade only partially reverses. Crucially, the principal metabolic stresses - accumulation of lactate, lipids and adenosine, deprivation of glucose and amino acids, and hypoxia - do not act in isolation but form a densely cross-regulated network that progressively reinforces T cell exhaustion. This review synthesizes how each barrier arises and how they amplify one another, then maps nanomaterial-based countermeasures onto this network: catalytic nanomaterials that degrade lactate and adenosine, lipid-modulating and mitochondria-targeted formulations, amino-acid replenishment systems, and hypoxia-relieving designs that pair metabolic correction with checkpoint inhibition or photodynamic therapy. Particular attention is given to the design principles - tissue targeting, stimuli-responsive release and rational combination - that determine whether metabolic reprogramming yields durable restoration of T cell function rather than transient phenotypic rescue. Emerging preclinical evidence indicates that nanomaterial-mediated metabolic remodeling can convert the immunosuppressive TME into an immune-supportive niche and recover effector function of exhausted T cells. We further identify the key gaps that currently limit clinical translation: the absence of subset-level evaluation distinguishing reversible progenitor-like exhausted T cells from terminally exhausted cells, the lack of epigenetic endpoints such as histone lactylation, off-target metabolic suppression of T cells themselves, and the manufacturing and safety hurdles of clinical-grade nanomaterials. Resolving these issues would establish metabolic reprogramming as a credible frontier for next-generation cancer immunotherapy.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pharmacy, School of Medicine & Health Sciences, Wuxi Taihu University, Wuxi, Jiangsu Province, People's Republic of China."
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Xiaoyan Zhu"
    },
    {
      "affs": [
        0
      ],
      "name": "Lin He"
    },
    {
      "affs": [
        0
      ],
      "name": "Jinwei Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Shuhui Guo"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaoxin Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Yongjing Cao"
    },
    {
      "affs": [
        0
      ],
      "name": "Shaozheng Song"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bctm2t5wf24bx.bib",
  "cited_by": 0,
  "doi": "10.2147/ijn.s639887",
  "fulltext_url": "https://europepmc.org/articles/PMC13682516",
  "id": "bctm2t5wf24bx",
  "issns": [
    "1176-9114",
    "1178-2013"
  ],
  "landing_url": "https://europepmc.org/article/MED/42903895",
  "language": "eng",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2730|Cancer Immunotherapy and Biomarkers"
    ]
  ],
  "openalex": "W7221920560",
  "pdf_url": "https://europepmc.org/articles/PMC13682516?pdf=render",
  "pmcid": "PMC13682516",
  "pmid": "42903895",
  "published": "2026-10-16",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/bctm2t5wf24bx.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:53Z",
      "native_id": "MED:42903895",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42903895"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Cancer Immunotherapy and Biomarkers",
      "subfield": "oncology"
    }
  ],
  "title": "Nanomaterials Reshaping Tumor Metabolism: A New Frontier to Overcome T Cell Exhaustion.",
  "title_text": "Nanomaterials Reshaping Tumor Metabolism: A New Frontier to Overcome T Cell Exhaustion.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:53Z",
  "url": "https://research.draconitic.com/paper/bctm2t5wf24bx",
  "venue": "International journal of nanomedicine",
  "versions": []
}