Evidence mapPaperPMID 42208538Full record

ArticleMed (New York, N.Y.)2026

Loss of tumor suppressor NF2 mediates resistance to CAR T cell and anti-PD-1 therapy: Strategies to restore immunotherapy sensitivity.

Miguel A Lopez-Lago, Meriem Taleb, Mehek Ningoo, Tomoyo Okada, Xiaoyu Li, Hyun-Sung Lee, Bryan M Burt, Michael Offin, Navin K Chintala, Prasad S Adusumilli

Abstract read
In one paragraph

Article in Med (New York, N.Y.), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

10 authors.

Miguel A Lopez-LagoThoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: miguel.lopezlago@gmail.com.
Meriem TalebThoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Mehek NingooThoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Tomoyo OkadaDepartment of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Xiaoyu LiThoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Hyun-Sung LeeDivision of Thoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA.
Bryan M BurtDivision of Thoracic Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 99095, USA.
Michael OffinThoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Navin K ChintalaThoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Prasad S AdusumilliThoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: adusumip@mskcc.org.

Funding

The Patient-Reported Outcomes, Community-Engagement and Language (PRO-CEL) CoreP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · 1985 to 2025
$88.4M
SURGICAL ONCOLOGY RESEARCH TRAINING PROGRAMT32CA009501 · SLOAN-KETTERING INSTITUTE FOR CANCER RES · 1985 to 2025
$1.7M
CD28-KITv CAR T cells with PD-1 dominant negative receptorUG3CA290241 · SLOAN-KETTERING INST CAN RESEARCH · 2025 to 2025
$1.6M
Tuning KITv CAR T cells for the solid tumor environmentR01CA292664 · SLOAN-KETTERING INST CAN RESEARCH · 2025 to 2025
$655k
NCI NIH HHS P30 CA008748NCI NIH HHS R01 CA235667NCI NIH HHS R01 CA236615NCI NIH HHS R01 CA292664NCI NIH HHS T32 CA009501NCI NIH HHS UG3 CA290241
6 · The paper itself

Abstract

backgroundInvestigating the biological mechanisms of acquired resistance to immunotherapy remains a necessity for effective treatment of solid tumors.

methodsDiffuse pleural mesothelioma (DPM) tumors, from immunocompetent and immunodeficient mouse models with acquired resistance to chimeric antigen receptor (CAR) T cell therapy were analyzed using flow cytometry, immunofluorescence, and ELISA. The interplay between genetic alterations in the cancer cell and site-specific tumor immune microenvironment (TIME) was characterized; therapies to reverse immunotherapy resistance were investigated.

findingsAnalysis of tumors with acquired resistance to CAR T cell therapy demonstrated lower expression of tumor suppressor NF2. Enforced depletion of NF2 promoted resistance to CAR T cell and anti-PD-1 therapy in DPM but not in heterotopic subcutaneous tumors. Loss of NF2 was associated with accumulation of immunosuppressive complement receptor of immunoglobulin superfamily (CRIg)

conclusionsOur study uncovers a previously unknown mechanism of resistance to immunotherapy by identifying the dynamic interplay between cancer cell genetic alterations and the TIME.

fundingThis research was funded in part through the NCI UG3CA290241, R01CA292664, R01CA235667, R01CA236615, and Department of War CA200437.

Indexed as

Drug Resistance, NeoplasmImmune Checkpoint InhibitorsImmunotherapy, AdoptiveMesotheliomaNeurofibromin 2Pleural NeoplasmsAnimalsCell Line, TumorHumansImmunotherapyMiceProgrammed Cell Death 1 ReceptorReceptors, Chimeric AntigenTumor MicroenvironmentImmune Checkpoint InhibitorsNeurofibromin 2NF2 protein, humanProgrammed Cell Death 1 ReceptorReceptors, Chimeric Antigenacquired resistanceCAR therapycheckpoint blockade therapyHippo pathwayimmunosupressionimmunotherapyPD-1 blockadePre-clinical researchTEAD inhibitorstumor-associated macrophagestumor suppressor

Identifiers

PMID42208538
PMCPMC13256109

What Socratic holds

Textmetadata
LicenceTDM
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.