Intratumoral pro-oxidants promote cancer immunotherapy by recruiting and reprogramming neutrophils to eliminate tumors

Ralph, Stephen John; Reynolds, Maxwell

doi:10.1007/s00262-022-03248-8

Cited by 5 publications

(4 citation statements)

References 156 publications

(204 reference statements)

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“…On the other hand, the high transcriptional overexpression of CCL17 , also called TARC , seems to have a complex effect on tumor immunity. Some studies have associated CCL17 with the N2 tumor-promoting subtype due to its role in immune suppression mediated by regulatory T cells [ 37 , 43 ]. However, CCL17 is also expressed specifically by neutrophils and macrophages and plays a significant role in the alternative cross-priming of dendritic cells (DCs), enabling them to trigger CD8 + T lymphocyte responses against tumor antigens [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Transcriptomics of Canine Inflammatory Mammary Cancer Treated with Empty Cowpea Mosaic Virus Implicates Neutrophils in Anti-Tumor Immunity

Barreno,

Sevane,

Valdivia

et al. 2023

IJMS

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Canine inflammatory mammary cancer (IMC) is a highly aggressive and lethal cancer in dogs serving as a valuable animal model for its human counterpart, inflammatory breast cancer (IBC), both lacking effective therapies. Intratumoral immunotherapy (IT-IT) with empty cowpea mosaic virus (eCPMV) nanoparticles has shown promising results, demonstrating a reduction in tumor size, longer survival rates, and improved quality of life. This study compares the transcriptomic profiles of tumor samples from female dogs with IMC receiving eCPMV IT-IT and medical therapy (MT) versus MT alone. Transcriptomic analyses, gene expression profiles, signaling pathways, and cell type profiling of immune cell populations in samples from four eCPMV-treated dogs with IMC and four dogs with IMC treated with MT were evaluated using NanoString Technologies using a canine immune-oncology panel. Comparative analyses revealed 34 differentially expressed genes between treated and untreated samples. Five genes (CXCL8, S100A9, CCL20, IL6, and PTGS2) involved in neutrophil recruitment and activation were upregulated in the treated samples, linked to the IL17-signaling pathway. Cell type profiling showed a significant increase in neutrophil populations in the tumor microenvironment after eCPMV treatment. These findings highlight the role of neutrophils in the anti-tumor response mediated by eCPMV IT-IT and suggest eCPMV as a novel therapeutic approach for IBC/IMC.

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Section: Discussionmentioning

confidence: 99%

Transcriptomics of Canine Inflammatory Mammary Cancer Treated with Empty Cowpea Mosaic Virus Implicates Neutrophils in Anti-Tumor Immunity

Barreno,

Sevane,

Valdivia

et al. 2023

IJMS

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“…A better knowledge of the specific mechanisms of N1 neutrophil activation, regulation, and recruitment is now required to fully leverage their antitumor potential against malignancies both locally and distantly. 58 Neutrophils thus appear to play a significant and varied role in tumor development, from initiation and progression of the primary tumor to the development and progression of distant metastases. 56 Although some research has been done on lymphocytes in isolation on tumor development, most studies in this area are in the context of variation of lymphocyte subsets in various tumors or the context of NLR.…”

Section: Discussionmentioning

confidence: 99%

Neutrophil-to-lymphocyte Ratio as an Effective Biomarker for Meningioma: A Systematic Review and Meta-analysis

Khanzadeh,

Azarhomayoun,

Rahmati

et al. 2023

Explor Res Hypothesis Med

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Background and objectives: Previous studies showed that tumors are associated with the increased inflammatory burden and neutrophil-to-lymphocyte ratio (NLR) is also associated with inflammatory conditions. However, there is no review on the role of NLR in meningioma. The goal of this study was to see if NLR has any prognostic and diagnostic value in meningioma. Methods:The search was conducted on PubMed, Scopus, and Web of Science up to 3 August 2023. A total of 23 studies were included in the systematic review, of which 13 were included in the meta-analysis.Results: It was found that patients with high-grade meningioma had higher levels of NLR compared to those with low-grade meningioma (standardized mean difference [SMD] = 0.72, 95% confidence interval [CI]: 0.21-1.23, p = 0.006)]. In addition, we found that there was no difference between NLR levels of patients with meningioma and those with gliomas (SMD, −0.19, 95% CI: −0.47-0.10, p = 0.20). Also, higher levels of NLR were found in patients with meningioma compared with healthy controls (SMD = 0.56, 95% CI: 0.24-0.88, p = 0.01). Studies showed that an NLR > 2.4 differentiated high-grade and low-grade meningioma, an NLR > 2.74 differentiated high and low progression-free survival groups, and an NLR > 2.59 was associated with recurrence, with high sensitivity and specificity. However, the NLR did not predict postoperative pneumonia following meningioma resection. Because of the contradiction, our study did not clearly demonstrate the difference in NLR levels in meningioma and other pathologies, so more studies are needed on this subject.Conclusions: NLR had significant diagnostic and prognostic value in meningioma. In general, we inferred a strong link between systemic inflammation assessed by NLR and meningioma, based on elevated levels of NLR in patients with meningioma compared to healthy controls. In addition, NLR had significant predictive potential for the progression and recurrence of meningioma. The predictive potential increased when combined with other diagnostic tools such as fibrinogen level. NLR may guide clinical decision making as an inflammatory marker and its relationship to therapeutic efficacy.

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“…LDNs that have an immature phenotype, show prevalence in the circulation of many cancers and participate in carcinogenesis and metastasis [ 100 ]. In the field of cancer immunotherapy, the stimulation of N1 neutrophils can mediate toxic impacts on cancer cells [ 108 ]. Furthermore, the stimulation of Ly6Ehi neutrophils through the STING pathway can enhance sensitivity to anti-PD-1 therapy, and they can be utilized as predictors of cancer immunotherapy [ 109 ].…”

Section: Tumor Microenvironment Componentsmentioning

confidence: 99%

Nanoparticles in tumor microenvironment remodeling and cancer immunotherapy

Lu,

Kou,

Lou

et al. 2024

J Hematol Oncol

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Cancer immunotherapy and vaccine development have significantly improved the fight against cancers. Despite these advancements, challenges remain, particularly in the clinical delivery of immunomodulatory compounds. The tumor microenvironment (TME), comprising macrophages, fibroblasts, and immune cells, plays a crucial role in immune response modulation. Nanoparticles, engineered to reshape the TME, have shown promising results in enhancing immunotherapy by facilitating targeted delivery and immune modulation. These nanoparticles can suppress fibroblast activation, promote M1 macrophage polarization, aid dendritic cell maturation, and encourage T cell infiltration. Biomimetic nanoparticles further enhance immunotherapy by increasing the internalization of immunomodulatory agents in immune cells such as dendritic cells. Moreover, exosomes, whether naturally secreted by cells in the body or bioengineered, have been explored to regulate the TME and immune-related cells to affect cancer immunotherapy. Stimuli-responsive nanocarriers, activated by pH, redox, and light conditions, exhibit the potential to accelerate immunotherapy. The co-application of nanoparticles with immune checkpoint inhibitors is an emerging strategy to boost anti-tumor immunity. With their ability to induce long-term immunity, nanoarchitectures are promising structures in vaccine development. This review underscores the critical role of nanoparticles in overcoming current challenges and driving the advancement of cancer immunotherapy and TME modification.

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Intratumoral pro-oxidants promote cancer immunotherapy by recruiting and reprogramming neutrophils to eliminate tumors

Cited by 5 publications

References 156 publications

Transcriptomics of Canine Inflammatory Mammary Cancer Treated with Empty Cowpea Mosaic Virus Implicates Neutrophils in Anti-Tumor Immunity

Transcriptomics of Canine Inflammatory Mammary Cancer Treated with Empty Cowpea Mosaic Virus Implicates Neutrophils in Anti-Tumor Immunity

Neutrophil-to-lymphocyte Ratio as an Effective Biomarker for Meningioma: A Systematic Review and Meta-analysis

Nanoparticles in tumor microenvironment remodeling and cancer immunotherapy

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