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

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

  • By

  • 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

  • Lilit Karapetyan

  • Nikhil I. Khushalani

  • Zeynep Eroglu

  • Ahmad A. Tarhini

  • James J. Mulé

  • Joseph Markowitz

  • June 22, 2026

  • 0 min

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Objective:

To examine how inducible nitric oxide synthase (iNOS) shapes the efficacy of anti–PD-1 therapy in melanoma, particularly through interferon signaling.

Approach:
    Key Findings:
    • Tumors grew significantly faster in iNOS KO mice, and anti–PD-1 therapy had no effect, indicating that iNOS-derived NO contributes to treatment efficacy.
    • NO donors inhibited melanoma proliferation and induced apoptosis in vitro.
    • Transcriptomic analysis showed anti–PD-1 upregulated interferon pathway genes in WT but not iNOS KO mice.
    • A NO-producing dendritic-cell subset was associated with improved PFS in melanoma patients (hazard ratio 0.453; 95% CI = 0.270-0.992; p=0.048).
    Interpretation:

    iNOS-derived NO is necessary for effective anti–PD-1 immunotherapy in melanoma, promoting interferon signaling and immune activation.

    Limitations:
    • The study primarily utilized murine models, which may not fully replicate human responses.
    • The sample size of melanoma patients analyzed was limited to 27.
    Conclusion:

    Loss of iNOS impairs tumor control and immune responsiveness, supporting NO as a potential biomarker and therapeutic adjunct in melanoma treatment.

Original Source(s)

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

  • by 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, Lilit Karapetyan, Nikhil I. Khushalani, Zeynep Eroglu, Ahmad A. Tarhini, James J. Mulé, Joseph Markowitz

  • June 22, 2026

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