Streptococcus anginosus-associated kynurenic acid drives PD-1 blockade resistance through an ITGA2-mTOR-CTSV axis in gastric cancer.

Ren Y, Yu X, Jiang J, Luo J, Zhao C, Mao X, Xi Y, He J, Yu C, Hu Y · 2026 · Journal for immunotherapy of cancer · Atlas ID REN2026

What this study shows

Tumor microbiota-derived kynurenic acid drives resistance to PD-1 blockade in gastric cancer through the ITGA2-mTOR-CTSV axis: kynurenic acid induces ITGA2 and inhibits an mTOR-dependent cascade, which sustains cathepsin V expression and suppresses CD8+ T cell cytotoxic function.

Abstract

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The tumor microbiota critically shapes responses to immunotherapy; however, the mechanisms by which specific microbial species drive immune checkpoint blockade (ICB) resistance in gastric cancer (GC) remain poorly defined. Bacterial enrichment was assessed in ICB-unresponsive GC tissues from patients and multiple preclinical models. Orthotopic, subcutaneous, and germ-free mono-colonized mouse models were employed to evaluate the impact on antitumor immunity and PD-1 blockade efficacy.

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: Mouse + Human (gastric cancer)); the code names the system studied -- animal work can be rigorous and still not be human data.
Study type	4 - Animal Study
Model system	Mouse + Human (gastric cancer)
Journal	Journal for immunotherapy of cancer
Year	2026
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1136/jitc-2026-015172 · PMID 42562425 · Free full text (PMC13448627)

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	ITGA2 targeting / anti-PD-1
Target	mTOR (ITGA2-mTOR-CTSV axis)
Model	Mouse + Human
Effect	Kynurenic acid induces ITGA2 and inhibits an mTOR-dependent cascade, sustaining cathepsin V and suppressing CD8+ T cells, driving immunotherapy resistance

In the Atlas

Cite this paper

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Ren, Y., Yu, X., Jiang, J., Luo, J., Zhao, C., Mao, X., Xi, Y., He, J., Yu, C., & Hu, Y. (2026). Streptococcus anginosus-associated kynurenic acid drives PD-1 blockade resistance through an ITGA2-mTOR-CTSV axis in gastric cancer. Journal for immunotherapy of cancer. https://doi.org/10.1136/jitc-2026-015172

@article{REN2026,
  author       = {Ren, Y. and Yu, X. and Jiang, J. and Luo, J. and Zhao, C. and Mao, X. and Xi, Y. and He, J. and Yu, C. and Hu, Y.},
  title        = {{Streptococcus anginosus-associated kynurenic acid drives PD-1 blockade resistance through an ITGA2-mTOR-CTSV axis in gastric cancer}},
  journal      = {Journal for immunotherapy of cancer},
  year         = {2026},
  doi          = {10.1136/jitc-2026-015172},
  note         = {PMID: 42562425},
}

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 REN2026) [Data set]. https://mtor-atlas.org/study/REN2026/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_REN2026,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record REN2026},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/REN2026/},
  doi          = {10.5281/zenodo.22059963}
}

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