Low-density neutrophils - A critical component in understanding the tumor microenvironment of oral squamous cell carcinoma

Sep 23, 2026

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Tumour microenvironment drives cancer progression and provides an avenue for immune evasion. Circulating neutrophils influence tumour growth and metastatic behaviour, and a phenotypic subset of low-density neutrophils (LDNs) has been linked to disease severity. This prospective study evaluates LDN and normal-density neutrophil (NDN) populations in oral cancer using CD16+ magnetic sorting, density-gradient separation, and flow cytometry. Oral squamous cell carcinoma patients show altered LDN/NDN ratios and elevated neutrophil-to-lymphocyte ratios, supporting prognosis and diagnosis.

LanguageEnglish

CategoryHealthcare

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Pages7

Reading Time18 min

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Abstract

Introduction

Oral squamous cell carcinoma background

Risk factors and diagnosis

Tumor microenvironment and neutrophils

| Original Article | | | --- | --- | | | | | Low‑density neutrophils: A critical component in understanding the tumor microenvironment of oralsquamous cell carcinoma
Thayalan Dineshkumar1, Nirmala Anandan2, Rajkumar Krishnan1, Indumathi Nandhakumar1 Departments of 1Oral Pathology and Microbiology and 2 Biochemistry, SRM Dental College, Ramapuram, Chennai, Tamil Nadu, India | | | | | | Abstract
Background: Tumour microenvironment is one of the evading research studies in the progression of cancers. Circulating neutrophil’s contribution to tumor growth and metastatic progression has been a matter of research interest. The phenotypic subset of low‑density neutrophils (LDNs) has been seen as closely associated with disease severity in various cancers.
Aim and Objectives: This study aims to investigate the LDN and normal‑density neutrophil (NDN) populations in oral cancer.
Materials and Methods: This is prospective research in which the CD16+ population was magnetically sorted and leukocytes were separated in a density gradient. Using a flow cytometer, the percentages of the neutrophil subpopulation were ascertained. It was established that there are two distinct populations of human neutrophils: LDNs and NDNs.
Results: Patients with oral squamous cell carcinoma (OSCC) showed a higher percentage of LDN/NDN ratio and a correspondingly lower percentage of LDN/NDN ratio when compared to the control group. In addition, patients with OSCC had higher neutrophil‑to‑lymphocyte ratios (NLRs) .
Conclusion: The current study showed a significant correlation between the LDN/NDN ratio in OSCC, which could be used as a benchmark for novel treatments. Additionally, the acquired LDNs/NDNs and NLR levels in cancer patients demonstrate their importance in OSCC patient prognosis and diagnosis.
Keywords: Low‑density neutrophils, neutrophils, normal‑density neutrophils, oral squamous cell carcinoma | | | Address for correspondence: Prof. Nirmala Anandan, Department of Biochemistry, SRM Dental College, Ramapuram Campus, Chennai ‑ 600 089, Tamil Nadu, India.
E‑mail: [nirmalaa@srmist.edu.in](nirmalaa@srmist.edu.in)
Submitted: 18‑Dec‑2024, Revised: 20‑Mar‑2025, Accepted: 25‑Mar‑2025, Published: 30‑Jun‑2025 | | INTRODUCTION Oral squamous cell carcinoma (OSCC) is a highly prevalent and aggressive cancer of the head and neck, accounting for over 90% of oral malignancies. Globally, its prevalence varies, with higher rates associated with alcohol and tobacco use.[1,2] Because of its high rates of morbidity and mortality, | Access this article online | | | --- | --- | | Quick Response Code: | Website:
[https://journals.lww.com/JPAT/](https://journals.lww.com/JPAT/) | | | | | | DOI:
10.4103/jomfp.jomfp_351_24 | OSCC continues to be a major public health concern even with advances in research and therapy. Studies show that the 5‑year survival rate for early‑stage OSCC is about 80% and that it drops to about 30% in later stages; therefore, early identification is critical. [3] The pathophysiology of OSCC is complex, encompassing genetic, environmental, This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non‑commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms. For [reprints contact:](reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com)[ WKHLRPMedknow_reprints@wolterskluwer.com](reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com) How to cite this article: Dineshkumar T, Anandan N, Krishnan R, Nandhakumar I . Low‑density neutrophils: A critical component in understanding the tumor microenvironment of oral squamous cell carcinoma. J Oral Maxillofac Pathol 2025;29:172‑8 . 172 © 2025 Journal of Oral and Maxillofacial Pathology | Published by Wolters Kluwer-Medknow Dineshkumar,

FAQs

What was the study’s main aim regarding neutrophil populations in oral cancer?

To investigate low-density neutrophils (LDNs) and normal-density neutrophils (NDNs) populations in oral cancer.

How were LDN and NDN populations measured in the study?

CD16+ cells were magnetically sorted, leukocytes were separated in a density gradient, and flow cytometry was used to determine neutrophil subpopulation percentages.

What findings link LDN/NDN ratio and neutrophil-to-lymphocyte ratio to oral squamous cell carcinoma?

OSCC patients showed a higher LDN/NDN ratio (and a correspondingly lower ratio when compared to control) and higher neutrophil-to-lymphocyte ratios, indicating relevance for prognosis and diagnosis.

Sep 23, 2026

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