Multi-Dimensional Flow Cytometry Analyses Reveal a Dichotomous Role for Nitric Oxide in Melanoma Patients Receiving Immunotherapy

Saurabh K Garg; Matthew J Ott; A G M Mostofa; Zhihua Chen; Y Ann Chen; Jodi Kroeger; Biwei Cao; Adam W Mailloux; Alisha Agrawal; Braydon J Schaible; Amod Sarnaik; Jeffrey S Weber; Anders E Berglund; James J Mulé; Joseph Markowitz

doi:10.3389/fimmu.2020.00164

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Multi-Dimensional Flow Cytometry Analyses Reveal a Dichotomous Role for Nitric Oxide in Melanoma Patients Receiving Immunotherapy

Journal article

Open access

Peer reviewed

Multi-Dimensional Flow Cytometry Analyses Reveal a Dichotomous Role for Nitric Oxide in Melanoma Patients Receiving Immunotherapy

Saurabh K Garg, Matthew J Ott, A G M Mostofa, Zhihua Chen, Y Ann Chen, Jodi Kroeger, Biwei Cao, Adam W Mailloux, Alisha Agrawal, Braydon J Schaible, …

Frontiers in immunology, Vol.11, pp.164-164

2020

DOI: 10.3389/fimmu.2020.00164

PMCID: PMC7052497

PMID: 32161584

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https://doi.org/10.3389/fimmu.2020.00164View

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Abstract

Phenotyping of immune cell subsets in clinical trials is limited to well-defined phenotypes, due to technological limitations of reporting flow cytometry multi-dimensional phenotyping data. We developed a multi-dimensional phenotyping analysis tool and applied it to detect nitric oxide (NO) levels in peripheral blood immune cells before and after adjuvant ipilimumab co-administration with a peptide vaccine in melanoma patients. We analyzed inhibitory and stimulatory markers for immune cell phenotypes that were felt to be important in the NO analysis. The pipeline allows visualization of immune cell phenotypes without knowledge of clustering techniques and to categorize cells by association with relapse-free survival (RFS). Using this analysis, we uncovered the potential for a dichotomous role of NO as a pro- and anti-melanoma factor. NO was found in subsets of immune-suppressor cells associated with shorter-term (≤ 1 year) RFS, whereas NO was also present in immune-stimulatory effector cells obtained from patients with significant longer-term (> 1 year) RFS. These studies provide insights into the cell-specific immunomodulatory role of NO. The methods presented herein can be applied to monitor the pro- and anti-tumor effects of a variety of immune-based therapeutics in cancer patients. NCT00084656 (https://clinicaltrials.gov/ct2/show/NCT00084656).

Adult

Aged

Antineoplastic Agents, Immunological - therapeutic use

Cancer Vaccines - therapeutic use

Female

Flow Cytometry - methods

Humans

Immunity

Immunotherapy - methods

Ipilimumab - therapeutic use

Leukocytes, Mononuclear - immunology

Male

Melanoma - blood

Melanoma - immunology

Melanoma - therapy

Middle Aged

Nitric Oxide - immunology

Nitric Oxide - metabolism

Phenotype

Skin Neoplasms - blood

Skin Neoplasms - immunology

Skin Neoplasms - therapy

Vaccines, Subunit - therapeutic use

Young Adult

Details

Title: Subtitle: Multi-Dimensional Flow Cytometry Analyses Reveal a Dichotomous Role for Nitric Oxide in Melanoma Patients Receiving Immunotherapy
Creators: Saurabh K Garg - Moffitt Cancer Center
Matthew J Ott - Moffitt Cancer Center
A G M Mostofa - Moffitt Cancer Center
Zhihua Chen - Moffitt Cancer Center
Y Ann Chen - Moffitt Cancer Center
Jodi Kroeger - Moffitt Cancer Center
Biwei Cao - Moffitt Cancer Center
Adam W Mailloux - Moffitt Cancer Center
Alisha Agrawal - University of South Florida
Braydon J Schaible - Moffitt Cancer Center
Amod Sarnaik - University of South Florida
Jeffrey S Weber - NYU Langone Health
Anders E Berglund - Moffitt Cancer Center
James J Mulé - Moffitt Cancer Center
Joseph Markowitz - University of South Florida
Resource Type: Journal article
Publication Details: Frontiers in immunology, Vol.11, pp.164-164
DOI: 10.3389/fimmu.2020.00164
PMID: 32161584
PMCID: PMC7052497
NLM abbreviation: Front Immunol
ISSN: 1664-3224
eISSN: 1664-3224
Grant note: P30 CA076292 / NCI NIH HHS P50 CA168536 / NCI NIH HHS
Language: English
Date published: 2020
Academic Unit: Microbiology and Immunology
Record Identifier: 9984297332902771

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