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.

Abstract

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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 →

At a glance

Evidence type	A Animal model Marked A because it is an animal intervention or observation study measuring an organismal outcome (model: Syngeneic mouse models of TP53-mutant HNSCC); the code names the system studied -- animal work can be rigorous and still not be human data.
Study type	4 - Animal Study
Model system	Syngeneic mouse models of TP53-mutant HNSCC
Journal	Neoplasia
Year	2026
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1016/j.neo.2026.101350 · PMID 42570420

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

Intervention	Everolimus (mTOR inhibitor)
Target	mTOR / PI3K-AKT-mTOR axis; downstream HIF-1α/VEGFA, PD-1/PD-L1
Model	Mouse (syngeneic TP53-mutant HNSCC models)
Effect	Reprograms immune-cold tumor microenvironment to an immune-active state; suppresses tumor growth

In the Atlas

Cite this paper

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Nath, P., Khandelwal, A., Li, C., Moore-Medlin, T., Vasudevan, S. S., Alvarez, V. A., Franco, O. E., Gutkind, J. S., & Nathan, C. O. (2026). mTOR inhibition augments antitumor immune effector response by reprogramming the TP53-mutant, immune-cold HNSCC tumor microenvironment. Neoplasia. https://doi.org/10.1016/j.neo.2026.101350

@article{NAT2026,
  author       = {Nath, P. and Khandelwal, A. and Li, C. and Moore-Medlin, T. and Vasudevan, S. S. and Alvarez, V. A. and Franco, O. E. and Gutkind, J. S. and Nathan, C. O.},
  title        = {{mTOR inhibition augments antitumor immune effector response by reprogramming the TP53-mutant, immune-cold HNSCC tumor microenvironment}},
  journal      = {Neoplasia},
  year         = {2026},
  doi          = {10.1016/j.neo.2026.101350},
  note         = {PMID: 42570420},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record NAT2026) [Data set]. https://mtor-atlas.org/study/NAT2026/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_NAT2026,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record NAT2026},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/NAT2026/},
  doi          = {10.5281/zenodo.22059963}
}

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