Immunosuppressive low-density neutrophils in the blood of cancer patients display a mature phenotype

Sep 24, 2026

Uploaded by Aran

Human neutrophils in the tumor microenvironment associate with poor overall survival, prompting focus on the immunosuppressive properties of low-density neutrophils (LDN). This study identified two LDN types in lung cancer and ovarian carcinoma: CD45high LDN that suppressed T-cell proliferation and showed mature morphology, and CD45low LDN that was immature and non-suppressive. Classical normal-density neutrophils (NDN) from cancer patients also suppressed T-cell proliferation, while NDN from healthy donors did not, with limited transcriptomic differences. Immunosuppression therefore depends on neutrophil maturity rather than density.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages14

Reading Time35 min

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Introduction

Tumor microenvironment and neutrophils

Low-density neutrophils and clinical relevance

Neutrophil heterogeneity and differentiation

Results

NDN and LDN suppress T-cell proliferation in cancer patients

Research Article Immunosuppressive low-density neutrophils in the blood of cancer patients display a mature phenotype Christophe Vanhaver1,*, Frank Aboubakar Nana1,2,3,* , Nicolas Delhez1 , Mathieu Luyckx1,4,5, Thibault Hirsch1 , Alexandre Bayard1, Camille Houbion1, Nicolas Dauguet1, Alice Brochier6, Pierre van der Bruggen1 , Annika M Bruger1 The presence of human neutrophils in the tumor microenvironment is strongly correlated to poor overall survival. Most previous studies have focused on the immunosuppressive capacities of low-density neutrophils (LDN), also referred to as granulocytic myeloid-derived suppressor cells, which are elevated in number in the blood of many cancer patients. We observed two types of LDN in the blood of lung cancer and ovarian carcinoma patients: CD45high LDN, which suppressed T-cell proliferation and displayed mature morphology, and CD45low LDN, which were immature and non-suppressive. We simultaneously evaluated the classical normal-density neutrophils (NDN) and, when available, tumor-associated neutrophils. We observed that NDN from cancer patients suppressed T-cell proliferation, and NDN from healthy donors did not, despite few transcriptomic differences. Hence, the immunosuppression mediated by neutrophils in the blood of cancer patients is not dependent on the cells’ density but rather on their maturity. DOI 10.26508/lsa.202302332 | Received 23 August 2023 | Revised 26 October 2023 | Accepted 27 October 2023 | Published online 6 November 2023 Introduction Neutrophils, the most abundant leukocytes in the blood, are the ﬁ rst responders to sterile injury and microbial infection (Borregaard, 2010) . The presence of neutrophils within the tumor microenvironment is more strongly correlated with unfavorable outcomes for patients than the presence of any other leukocyte (Jensen et al, 2012; Gentles et al, 2015; Ye et al, 2019) . However, both antitumor and protumor functions of tumor-associated neutrophils (TAN) have been described (Shaul & Fridlender, 2021; Gungabeesoon et al, 2023) . In addition, elevated levels of low-density neutrophils (LDN) in the blood indicate poorer treatment outcomes and survival prognoses for cancer patients (Sade-Feldman et al, 2016; Lang et al, 2018; Wanget al, 2018). Focusing on protumor neutrophils in cancer patients could provide new strategies to enhance current immunotherapies, help predict the therapies’ efﬁcacy, or help clinicians individualize treatment plans (Nagaraj et al, 2010; Moses & Brandau, 2016; Shaulet al, 2020; Gondois-Rey et al, 2021). LDN are more frequent in the blood of cancer patients than in healthy donors (Cassetta et al, 2020) . However, isolation (e.g., ﬂow cytometry versus magnetic bead selection) and phenotyping strategies differ between studies (Cassetta et al, 2019). A multicenter study by the COST Action Mye-EUNITER applied the same staining and gating strategy to blood samples from patients with various cancer and autoimmune conditions, and found that LDN are more present in the blood of patients with some cancer types, including melanoma, compared with others, for example, ovarian cancers (Cassetta et al, 2020) . Studying neutrophils remains demanding because these cells have an average half-life of 18 h in humans and are cryosensitive (Tak et al, 2013; Trellakis et al, 2013; LahozBeneytez et al, 2016) . The paradigm that neutrophils are an entirely homogenous population with unique and speciﬁc functions has been overturned (reviewed in Scapini et al [2016], Shaul and Fridlender [2018], and Zilionis et al [2019]). Instead, neutrophils respond to environmental cues and adopt tissue-speciﬁc features (Mackey et al, 2019; Ballesteroset al, 2020; Montaldo et al, 2022). Neutrophil subsets seem to fall along a single differentiation pathway, meaning that subsets share many characteristics and may only be distinguished by properties such as density, maturity, and functions (Scapini et al, 2016; Blanter et al, 2021). Here, we c

FAQs

What two types of low-density neutrophils were identified in cancer patients?

The study observed CD45high LDN and CD45low LDN. CD45high LDN suppressed T-cell proliferation and showed mature morphology, while CD45low LDN were immature and non-suppressive.

Do immunosuppressive effects depend on neutrophil density?

No. The study found that immunosuppression in cancer patients was not dependent on density but rather on neutrophil maturity.

How did normal-density neutrophils from cancer patients compare with those from healthy donors?

NDN from cancer patients suppressed T-cell proliferation, whereas NDN from healthy donors did not, despite few transcriptomic differences.

Sep 24, 2026

Uploaded by Aran