Evidence map›Paper›PMID 42069723›Full record

ArticleNature communications2026

PTPN2 inhibition unleashes response to STING agonism in head and neck squamous cell cancer.

Zehua Li, Cong Fu, Kartik Sehgal, Ann Marie Egloff, Tran C Thai, Omar Avila Monge, Cun Lan Chuong, Yaiza Senent, Maia Shea Lineberry, Benjamin K Eschle and 16 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Trial
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

26 authors.

Zehua LiDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0001-6342-3324
Cong FuDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Kartik SehgalDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0003-4391-6943
Ann Marie EgloffDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Tran C ThaiDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Omar Avila MongeBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Cun Lan ChuongBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Yaiza SenentBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Maia Shea LineberryBelfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA, USA.
Benjamin K EschleBelfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA, USA.
Koji HarataniDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0002-1767-6854
Elena V IvanovaDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Marco CampisiDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0002-9288-5285
Navin R MahadevanDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
John D QuadarellaDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0009-0007-7473-9034
Patrick C GedeonDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0002-5387-1833
Jonathan D SchoenfeldDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0002-5119-0401
Michihisa KonoDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0002-8506-928X
Caroline G FaheyDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0003-4155-5662
Chayapatou ChayawattoBelfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA, USA.
Kenneth NgoBelfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0001-5511-2825
Cloud P PaweletzDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0002-2287-5663
Prafulla C GokhaleBelfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0002-1974-5921
Robert T MangusoBroad Institute of MIT and Harvard, Cambridge, MA, USA. rmanguso@broadinstitute.org.ORCID http://orcid.org/0000-0003-1336-413X
Ravindra UppaluriDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. ravindra_uppaluri@dfci.harvard.edu.ORCID http://orcid.org/0000-0001-5988-6828
David A BarbieDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. david_barbie@dfci.harvard.edu.

Funding

Defining mechanisms of immunotherapy resistance in head and neck squamous cell carcinomasU01DE029188 · NIDCR · DANA-FARBER CANCER INST · PI BARBIE, DAVID A, HADDAD, ROBERT I. · 2019 to 2019
$4.3M
Targeting the immunologic vulnerabilities of small cell lung carcinomaK08CA270077 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Navin Mahadevan · 2022 to 2026
$1.0M
NCI NIH HHS K08 CA270077U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01CA190294U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) U01DE029188
6 · The paper itself

Abstract

cGAS-STING signaling can promote antitumor immunity, and tumor cell STING is suppressed in a variety of cancer subtypes that resist immune checkpoint blockade. Although STING agonists have failed clinical trials, precision approaches targeting restoration of tumor cell STING expression have yet to be explored. Here, we report that head and neck squamous cell cancer (HNSCC) exhibits a mechanism of STING suppression related to upregulation of protein tyrosine phosphatase non-receptor (PTPN) type 2 (PTPN2) that is also evident in other cancers. PTPN2 inhibition (PTPN2i) increases HNSCC tumor cell STING by restoring IFNγ-STAT1-mediated induction of STING mRNA. This restores sensitivity to STING agonism and natural killer cell activation, suppressing tumor growth in an immune cell-dependent manner in anti-PD-1 refractory syngeneic HNSCC mouse tumor models in female mice. Together, these findings demonstrate that PTPN2i can unleash STING agonist response, providing a rationale for the evaluation of this therapeutic combination in HNSCC and potentially other cancer types.

Indexed as

Head and Neck NeoplasmsMembrane ProteinsProtein Tyrosine Phosphatase, Non-Receptor Type 2Squamous Cell Carcinoma of Head and NeckAnimalsCell Line, TumorcGAS-STING Signaling PathwayFemaleGene Expression Regulation, NeoplasticHumansInterferon-gammaKiller Cells, NaturalMiceMice, Inbred C57BLSignal TransductionSTAT1 Transcription FactorInterferon-gammaMembrane ProteinsProtein Tyrosine Phosphatase, Non-Receptor Type 2PTPN2 protein, humanSTAT1 Transcription FactorSTING1 protein, humanSting1 protein, mouseSTING Protein

Identifiers

PMID42069723
PMCPMC13342608

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.