Evidence map›Paper›PMID 42816487›Full record

ArticleNature communications2026

IFN-γ-driven iNOS induction in macrophages mediates CAR T cell resistance in B cell lymphoma.

Sae Bom Lee, Allan Pavy, Nolan Beatty, Justin C Boucher, Jay K Mandula, Emiliano Roselli, Darwin C Chang, Rachel V Jimenez, Hiroshi Kotani, Kayla Reid and 23 more

Abstract read
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. 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

5 · Who and what money

Authors and funding

33 authors.

Sae Bom LeeDepartment of Immunology, H. Lee Moffitt Cancer Center, Tampa, FL, USA.
Allan PavyDepartment of Medicine, Roswell Park Cancer Center, Buffalo, NY, USA.ORCID 0000-0002-2919-8706
Nolan BeattyDepartment of Immunology, H. Lee Moffitt Cancer Center, Tampa, FL, USA.
Justin C BoucherDepartment of Immunology, H. Lee Moffitt Cancer Center, Tampa, FL, USA.ORCID 0009-0008-8936-0470
Jay K MandulaDepartment of Immunology, H. Lee Moffitt Cancer Center, Tampa, FL, USA.
Emiliano RoselliDepartment of Clinical Science, H. Lee Moffitt Cancer Center, Tampa, FL, USA.
Darwin C ChangDepartment of Immunology, H. Lee Moffitt Cancer Center, Tampa, FL, USA.
Rachel V JimenezDepartment of Immunology, H. Lee Moffitt Cancer Center, Tampa, FL, USA.ORCID 0000-0003-2510-2268
Hiroshi KotaniDivision of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa, Japan.ORCID 0000-0002-6001-0636
Kayla ReidDepartment of Clinical Science, H. Lee Moffitt Cancer Center, Tampa, FL, USA.
Julio Vazquez-MartinezDepartment of Immunology, H. Lee Moffitt Cancer Center, Tampa, FL, USA.ORCID 0000-0002-8947-5971
Payal GoalaDepartment of Immunology, H. Lee Moffitt Cancer Center, Tampa, FL, USA.
Max IleckiDepartment of Medicine, Roswell Park Cancer Center, Buffalo, NY, USA.
Cooper J SailerDepartment of Medicine, Roswell Park Cancer Center, Buffalo, NY, USA.ORCID 0000-0001-8055-588X
Shannon L McSainDepartment of Medicine, Roswell Park Cancer Center, Buffalo, NY, USA.ORCID 0009-0002-2538-9983
Showkat HamidDepartment of Medicine, Roswell Park Cancer Center, Buffalo, NY, USA.
Muhammad Junaid TariqDepartment of Medicine, Roswell Park Cancer Center, Buffalo, NY, USA.ORCID 0000-0002-8495-8480
Rosa A Sierra-MondragonDepartment of Immunology, H. Lee Moffitt Cancer Center, Tampa, FL, USA.ORCID 0000-0002-1797-3867
Min LiuProteomics and Metabolomics Core, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
John M KoomenProteomics and Metabolomics Core, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.ORCID 0000-0002-3818-1762
Jonathan NguyenProteomics and Metabolomics Core, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.ORCID 0000-0001-6146-2047
Mohammad HussainiDepartment of Pathology, H. Lee Moffitt Cancer Center, Tampa, FL, USA.
Timothy I ShawDepartment of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center, Tampa, FL, USA.ORCID 0000-0002-9316-1924
Xuefeng WangDepartment of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center, Tampa, FL, USA.ORCID 0000-0001-5775-408X
Jianmin WangDepartment of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.ORCID 0000-0001-7527-0409
Julieta Abraham-MirandaDepartment of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center, Tampa, FL, USA.
Rawan FaramandDepartment of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center, Tampa, FL, USA.
Michael D JainDepartment of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center, Tampa, FL, USA.ORCID 0000-0002-7789-1257
Meredith L StoneDepartment of Medicine, Roswell Park Cancer Center, Buffalo, NY, USA.
Frederick L LockeCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.ORCID 0000-0001-9063-6691
Paulo C RodriguezDepartment of Immunology, H. Lee Moffitt Cancer Center, Tampa, FL, USA.ORCID 0000-0001-7480-6566
Yun Pyo KangCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.ORCID 0000-0002-1149-0880
Marco L DavilaDepartment of Clinical Science, H. Lee Moffitt Cancer Center, Tampa, FL, USA. Marco.Davila@RoswellPark.org.ORCID 0000-0002-6270-3065

Funding

Two-Spirit Films in Indigenous Cancer HealthP30CA016056 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI CANDACE S JOHNSON · 1985 to 2026
$116.6M
TRANSLATIONAL RESEARCHP30CA076292 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI John L. Cleveland · 1998 to 2026
$93.5M
Project 4P01CA250984 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI RODRIGUEZ, PAULO CESAR · 2021 to 2025
$10.1M
Neurocognitive and Patient-Reported Outcomes after Chimeric Antigen Receptor T-Cell Therapy: A Controlled ComparisonR01CA244328 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI HEATHER S.L. JIM, Frederick Locke · 2022 to 2026
$3.8M
Targeting CD83 to reduce leukemia relapse and GVHD after allogeneichematopoietic cell transplantationR01HL167232 · NHLBI · UNIVERSITY OF MINNESOTA · PI Brian C Betts, Marco L. Davila · 2023 to 2026
$2.8M
Plant-derived extracts regulate immunosuppressive myelopoiesis in Breast cancer patientsR01CA262121 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI RODRIGUEZ, PAULO CESAR · 2021 to 2025
$2.1M
Functional reprogramming of tumor-MDSC through antibody-based therapies targeting Notch ligandsR01CA233512 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI RODRIGUEZ, PAULO CESAR · 2019 to 2023
$2.0M
Stress Pathways in Tumors Drive Global MDSC Activity and Survival through ChopR01CA184185 · NCI · LSU HEALTH SCIENCES CENTER · PI RODRIGUEZ, PAULO CESAR · 2015 to 2019
$1.8M
NCI NIH HHS P01 CA250984NCI NIH HHS P30 CA016056NCI NIH HHS P30 CA076292NCI NIH HHS R01 CA184185NCI NIH HHS R01 CA233512NCI NIH HHS R01 CA244328NCI NIH HHS R01 CA262121NHLBI NIH HHS R01 HL167232U.S. Department of Health & Human Services | NIH | Center for Information Technology (Center for Information Technology, National Institutes of Health) 5R01HL167232
6 · The paper itself

Abstract

Chimeric antigen receptor (CAR) T cell therapies have revolutionized B cell malignancy treatment, but many patients with large B cell lymphoma (LBCL) experience primary resistance or relapse. To uncover resistance mechanisms, here we examine pre-infusion tumor biopsies and observe that increased immunoregulatory macrophages correlate with poor clinical responses. In murine models, CAR T cell-produced interferon-gamma (IFN-γ) upregulates inducible nitric oxide synthase (iNOS, NOS2) in immunoregulatory macrophages, impairing CAR T cell function. Proteomic profiling reveals that iNOS-expressing macrophages promote apoptosis and cell cycle arrest while downregulating protein synthesis machinery in CAR T cells. Metabolically, CAR T cells exhibit reduced glycolytic intermediates and altered tricarboxylic acid (TCA) cycle activity. Pharmacological inhibition of iNOS enhances CAR T cell treatment efficacy in vivo. Elevated levels of iNOS

Indexed as

Immunotherapy, AdoptiveInterferon-gammaLymphoma, B-CellMacrophagesNitric Oxide Synthase Type IIReceptors, Chimeric AntigenAnimalsApoptosisCell Line, TumorFemaleHumansMiceT-LymphocytesInterferon-gammaNitric Oxide Synthase Type IIReceptors, Chimeric Antigen

Identifiers

PMID42816487
PMCPMC13627683

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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.