Evidence map›Paper›PMID 42440610›Full record

ArticleFrontiers in immunology2026

iNOS is a key mediator of anti-PD-1 melanoma therapy response.

Quang Tam Nguyen, Youngchul Kim, Thi Hong Nga Le, Saurabh Garg, Vishanna Balkaran, Trisha Bhathivi, Alejandra Chamizo, Christopher W Dukes, Kimberly Ward, Andrew S Brohl and 6 more

Abstract read
In one paragraph

Article in Frontiers in immunology, 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

16 authors.

Quang Tam NguyenDepartment of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, United States.
Youngchul KimThe Immuno-Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, United States.
Thi Hong Nga LeDepartment of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, United States.
Saurabh GargThe Immuno-Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, United States.
Vishanna BalkaranDepartment of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, United States.
Trisha BhathiviDepartment of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, United States.
Alejandra ChamizoDepartment of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, United States.
Christopher W DukesDepartment of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, United States.
Kimberly WardDepartment of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, United States.
Andrew S BrohlDepartment of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, United States.
Lilit KarapetyanDepartment of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, United States.
Nikhil I KhushalaniDepartment of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, United States.
Zeynep ErogluDepartment of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, United States.
Ahmad A TarhiniDepartment of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, United States.
James J MuléDepartment of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, United States.
Joseph MarkowitzDepartment of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, United States.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Inducible nitric oxide synthase (iNOS) and its product nitric oxide (NO) were historically linked to poor melanoma outcomes, yet recent evidence shows NO supports anti-tumor immunity. This study examines how iNOS shapes anti-PD-1 efficacy, particularly through interferon signaling. Methods: B16-D5 melanoma tumors were implanted in wild-type (WT) and iNOS knockout (KO) mice to compare tumor growth and response to anti-PD-1 therapy. Flow cytometry, apoptosis assays, and RNA sequencing assessed NO production, PD-L1 expression, and interferon-related gene activation. Results: Tumors grew significantly faster in iNOS KO mice, and anti-PD-1 therapy had no effect, demonstrating that iNOS-derived NO contributes to treatment efficacy. NO donors inhibited melanoma proliferation and induced apoptosis Conclusion: iNOS-derived NO is necessary for effective anti-PD-1 immunotherapy in melanoma, promoting interferon signaling and immune activation. Loss of iNOS impairs tumor control and immune responsiveness, supporting NO as a potential biomarker and therapeutic adjunct to be explored while challenging assumptions about its deleterious role in melanoma.

Indexed as

Immune Checkpoint InhibitorsMelanomaMelanoma, ExperimentalNitric Oxide Synthase Type IIProgrammed Cell Death 1 ReceptorAnimalsApoptosisCell Line, TumorCell ProliferationFemaleHumansMiceMice, Inbred C57BLMice, KnockoutNitric OxideSignal TransductionImmune Checkpoint InhibitorsNitric OxideNitric Oxide Synthase Type IINos2 protein, mouseProgrammed Cell Death 1 Receptoranti-PD-1immunotherapyiNOSmelanomanitric oxide

Identifiers

PMID42440610
PMCPMC13333588

What OpenQuestion 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 OpenQuestion graph.