Oliver's mTOR Atlas Evidence Platform
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mTOR inhibition augments antitumor immune effector response by reprogramming the TP53-mutant, immune-cold HNSCC tumor microenvironment

Nath P; Khandelwal A; Li C; Moore-Medlin T; Vasudevan SS; Alvarez VA; Franco OE; Gutkind JS; Nathan CO · 2026 · Neoplasia · Atlas ID NAT2026

What this study shows

In syngeneic TP53-mutant HNSCC mouse models, the mTOR inhibitor everolimus reprogrammed the immune-cold tumor microenvironment: it increased CD8+ T cell and dendritic cell infiltration, reduced Tregs and HIF-1α/VEGFA-driven MDSC recruitment, boosted TNF-α/CXCL10 chemokine signaling, and reduced PD-1/PD-L1 expression — restoring T-cell cytotoxic competence and suppressing tumor growth.

Tier C because it is an animal intervention or observation study measuring an organismal outcome (model: Syngeneic mouse models of TP53-mutant HNSCC); tier describes study design, not quality -- animal evidence can be rigorous and still sit below direct human data.

At a glance

Evidence tierC Animal in vivo
Study type4 - Animal Study
Model systemSyngeneic mouse models of TP53-mutant HNSCC
JournalNeoplasia
Year2026
Peer reviewedYes
Record last updated2026-08-22
SourceDOI 10.1016/j.neo.2026.101350 · PMID 42570420

Extracted findings

InterventionEverolimus (mTOR inhibitor)
TargetmTOR / PI3K-AKT-mTOR axis; downstream HIF-1α/VEGFA, PD-1/PD-L1
ModelMouse (syngeneic TP53-mutant HNSCC models)
EffectReprograms immune-cold tumor microenvironment to an immune-active state; suppresses tumor growth

In the Atlas

Related topics

mTOREverolimusAkt/PKBPI3KTumor growth

Abstract

Resistance to immunotherapy remains a major clinical challenge in TP53-mutant head and neck squamous cell carcinoma (HNSCC), a disease subset characterized by immune exclusion, high recurrence, and poor outcomes. Given the constitutive activation of PI3K/AKT/mTOR signaling in TP53-mutant HNSCC and its role in disease progression, we investigated whether mTOR inhibition (mTORi) could overcome immune resistance and improve outcomes. Read the full abstract on PubMed →

Cite this record

Barton, O. (2026). mTOR inhibition augments antitumor immune effector response by reprogramming the TP53-mutant, immune-cold HNSCC tumor microenvironment — evidence-graded record NAT2026. In Oliver's mTOR Atlas. https://mtor-atlas.org/study/NAT2026/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_NAT2026,
  author       = {Barton, Oliver},
  title        = {{mTOR inhibition augments antitumor immune effector response by reprogramming the TP53-mutant, immune-cold HNSCC tumor microenvironment} --- evidence-graded record NAT2026},
  howpublished = {Oliver's mTOR Atlas},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/NAT2026/},
  note         = {Dataset DOI: 10.5281/zenodo.22059963}
}

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