Evidence map›Paper›PMID 41673019›Full record

ArticleNature communications2026

NKG2D upregulation sensitizes tumors to combined anti-PD1 and anti-VEGF therapy and prevents hearing loss.

Simeng Lu, Zhenzhen Yin, Limeng Wu, Yao Sun, Jie Chen, Lai Man Natalie Wu, Janet L Oblinger, Day C Blake, Bingyu Xiu, Lukas D Landegger and 8 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 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
–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

3 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Article
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

18 authors.

Simeng Lu *Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Zhenzhen Yin *Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Limeng WuEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Yao SunEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Jie ChenEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Lai Man Natalie WuMedpace Inc., Cincinnati, OH, USA.
Janet L OblingerCenter for Childhood Cancer, Abigail Wexner Research Institute at Nationwide Children's Hospital and Department of Pediatrics, The Ohio State University, Columbus, OH, USA.
Day C BlakeEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Bingyu XiuEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Lukas D LandeggerDepartment of Otolaryngology - Head and Neck Surgery and Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.
Richard SeistDepartment of Otolaryngology - Head and Neck Surgery and Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.
William HoEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-1272-8184
Adam P JonesEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Alona MuzikanskyBiostatistics Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Konstantina M StankovicDepartment of Otolaryngology - Head and Neck Surgery and Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.
Scott R PlotkinDepartment of Neurology and Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Long-Sheng ChangCenter for Childhood Cancer, Abigail Wexner Research Institute at Nationwide Children's Hospital and Department of Pediatrics, The Ohio State University, Columbus, OH, USA.ORCID http://orcid.org/0000-0002-5178-2992
Lei XuEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. lexu@mgh.harvard.edu.ORCID http://orcid.org/0000-0003-0525-183X

Funding

Co-Targeting IL-6 and EGFRsignaling for the Treatment of Schwannomatosis and Associated PainR01NS126187 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI JIANREN MAO, Lei Xu · 2023 to 2026
$1.8M
Targeting HMGB1 to improve hearing andenhance therapy for Vestibular SchwannomasR01DC020724 · NIDCD · MASSACHUSETTS GENERAL HOSPITAL · PI Konstantina M Stankovic, Lei Xu · 2023 to 2026
$1.8M
NIDCD NIH HHS R01 DC020724NINDS NIH HHS R01 NS126187United States Department of Defense | United States Army | Army Medical Command | Congressionally Directed Medical Research Programs (CDMRP) W81XWH-16-1-0219United States Department of Defense | United States Army | Army Medical Command | Congressionally Directed Medical Research Programs (CDMRP) W81XWH-20-1-0222U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) R01-NS126187U.S. Department of Health & Human Services | NIH | National Institute on Deafness and Other Communication Disorders (NIDCD) R01-DC020724
6 · The paper itself

Abstract

NF2-related schwannomatosis (NF2-SWN) is a debilitating condition, characterized by bilateral vestibular schwannomas (VSs) that progressively cause irreversible sensorineural hearing loss. Current management relies on surgery or radiotherapy, while bevacizumab (αVEGF) is used off-label, with variable and often transient efficacy. Effective therapies that durably suppress tumor growth and preserve hearing are urgently needed. Although immune checkpoint inhibitors have transformed cancer treatment, their efficacy in non-malignant tumors such as VS remains unclear. Here, we evaluate combined anti-PD1 (αPD1) and αVEGF therapy in two syngeneic, immune-competent VS models. Combination treatment significantly outperforms either monotherapy, inhibiting tumor growth and preventing hearing loss. Mechanistically, αVEGF enhances αPD1 efficacy by normalizing tumor vasculature, improving drug delivery and immune cell infiltration, and promoting cytotoxicity of T and NK cells via NKG2D upregulation. Combined treatment effectively controls tumor growth that progresses despite anti-VEGF therapy. These findings support αPD1 and αVEGF combination therapy as a promising strategy for NF2-SWN.

Indexed as

BevacizumabHearing LossNK Cell Lectin-Like Receptor Subfamily KProgrammed Cell Death 1 ReceptorVascular Endothelial Growth Factor AAnimalsCell Line, TumorFemaleHumansImmune Checkpoint InhibitorsKiller Cells, NaturalMiceMice, Inbred C57BLNeuroma, AcousticUp-RegulationBevacizumabImmune Checkpoint InhibitorsKlrk1 protein, mouseNK Cell Lectin-Like Receptor Subfamily KPdcd1 protein, mouseProgrammed Cell Death 1 ReceptorVascular Endothelial Growth Factor A

Identifiers

PMID41673019
PMCPMC12894996

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.