Search Results (40)

Fusobacterium nucleatum (F. nucleatum), a Gram-negative anaerobe traditionally associated with periodontal disease, has recently emerged as a putative contributor to gastric carcinoma (GC) pathogenesis. Beyond its detection in gastric tissues, particularly in patients negative for Helicobacter pylori (H. pylori) or in advanced GC cases, F. nucleatum exerts diverse oncogenic effects. It promotes GC progression by modulating the tumor microenvironment through IL−17/NF-κB signaling, inducing tumor-associated neutrophils (TANs), upregulating PD-L1 expression, and enhancing immune evasion. Moreover, it increases tumor invasiveness via cytoskeletal reorganization, while extracellular vesicles (EVs) induced by the infection contribute to tumor cell proliferation, invasion, and migration. Clinically, its presence correlates with increased tumor mutational burden (TMB), venous thromboembolism, and poor prognosis. This review summarizes the current evidence regarding the emerging role of F. nucleatum in gastric tumorigenesis, examines its potential utility as a diagnostic and prognostic biomarker within the framework of precision oncology, and outlines the molecular methodologies presently employed for its detection in gastric tissue specimens. Full article

Neutrophils are increasingly recognized as key players in the tumor microenvironment (TME), displaying functional plasticity that enables them to either promote or inhibit cancer progression. Depending on environmental cues, tumor-associated neutrophils (TANs) may polarize toward antitumor “N1” or protumor “N2” phenotypes, exerting diverse effects on tumor growth, metastasis, immune modulation, and treatment response. While previous studies have focused on the pathological roles of TANs in cancer, less attention has been given to how cancer therapies themselves influence the behavior of TANs. This review provides a comprehensive synthesis of current knowledge regarding the dynamics of TANs in response to major cancer treatment modalities, including chemotherapy, radiotherapy, cell-based immunotherapies, and oncolytic viral and bacterial therapies. We discuss how these therapies influence TAN recruitment, polarization, and effector functions within the TME, and highlight key molecular regulators involved. By consolidating mechanistic and translational insights, this review emphasizes the potential to therapeutically reprogram TANs to enhance treatment efficacy. A deeper understanding of context-dependent TAN roles will be essential for developing more effective, neutrophil-informed cancer therapies. Full article

This review delves into the characteristics of lipid metabolism reprogramming in cancer cells and immune cells within the tumor microenvironment (TME), discussing its role in tumorigenesis and development and analyzing the value of lipid metabolism-related molecules in tumor diagnosis and prognosis. Cancer cells support their rapid growth through aerobic glycolysis and lipid metabolism reprogramming. Lipid metabolism plays distinct roles in cancer and immune cells, including energy supply, cell proliferation, angiogenesis, immune suppression, and tumor metastasis. This review focused on shared lipid metabolic enzymes and transporters, lipid metabolism-related oncogenes and non-coding RNAs (ncRNAs) involved in cancer cells, and the influence of lipid metabolism on T cells, dendritic cells (DCs), B cells, tumor associated macrophages (TAMs), tumor associated neutrophils (TANs), and natural killer cells (NKs) within TME. Additionally, the role of lipid metabolism in tumor diagnosis and prognosis was explored, and lipid metabolism-based anti-tumor treatment strategies were summarized, aiming to provide new perspectives for achieving precision medicine. Full article

Cancer cells are often described as voracious consumers of nutrients, with glucose frequently cited as a key energy source; however, their metabolic plasticity allows them to adapt and utilize various substrates, including lipids and amino acids, to sustain growth and survival. However, the metabolic demands of immune cells within the tumor microenvironment (TME) are less commonly discussed despite their critical role in shaping the immune response. In this review, we explored the intricate interplay between immunometabolism and innate immunity cells in gastrointestinal cancers. We focused on how metabolic pathways, including glycolysis, fatty acid oxidation, and amino acid metabolism, drive the immunosuppressive functions of myeloid-derived suppressor cells (MDSCs) and tumor-associated neutrophils (TANs), tumor-associated macrophages (TAMs) and innate lymphocyte subsets such as NK cells. These cells contribute to a hostile immune landscape, supporting tumor growth and evasion from immune surveillance in a phenomenon of tumor-derived immunosuppression. Additionally, we investigated the influence of dietary interventions on the metabolic reprogramming of these immune cells, highlighting how nutrition can modulate the TME. Finally, we discussed emerging therapeutic strategies that target metabolic vulnerabilities in MDSCs, TANs, NK cells, and monocytes, offering a novel avenue for enhancing antitumor immunity. By dissecting these mechanisms, we aim to provide insights into how metabolic pathways can be harnessed to improve cancer treatment outcomes. This review underscores the importance of understanding immunometabolism not only as a driver of immune suppression but also as a potential therapeutic target in gastrointestinal cancer. Full article

Neutrophils, the most abundant circulating white blood cells, are essential for the initial immune response to infection and injury. Emerging research reveals a dualistic function of neutrophils in cancer, where they can promote or inhibit tumor progression. This dichotomy is influenced by the tumor microenvironment, with neutrophils capable of remodeling the extracellular matrix, promoting angiogenesis, or alternatively inducing cancer cell death and enhancing immune responses. An intriguing yet poorly understood aspect of neutrophil–cancer interactions is the phenomenon of neutrophil engulfment by cancer cells, which has been observed across various cancers. This process, potentially mediated by LC3-associated phagocytosis (LAP), raises questions about whether it serves as a mechanism for immune evasion or contributes to tumor cell death through pathways like ferroptosis. This review examines current knowledge on neutrophil development, their roles in cancer, and the mechanisms of LAP in neutrophil engulfment by tumor cells. We discuss how manipulating LAP impacts cancer progression and may represent a therapeutic strategy. We also explore neutrophils’ potential as delivery vehicles for cancer therapeutic agents. Understanding the complex functions of tumor-associated neutrophils (TANs) and the molecular mechanisms underlying LAP in cancer may open new avenues for effective therapeutic interventions and mitigate potential risks. Full article

In canine mammary neoplasms, greater inflammation is associated with higher histological grade, lymphatic invasion, and metastases. This retrospective study assessed the density of peri- and intratumoral tumor-infiltrating lymphocytes (TILs), tumor-associated neutrophils (TANs), and CD3⁺ and CD79⁺ lymphocytes in canine mammary neoplasms with a solid arrangement, and associated such data with histological types, immunophenotype, prognostic factors, cyclooxygenase-2 (Cox-2) expression and overall and cancer-specific survival. Sixty-one neoplasms with a solid arrangement were classified as malignant myoepitheliomas (6/9.8%), solid papillary carcinomas (8/13.1%), carcinomas with a solid pattern (9/14.8%), basaloid carcinomas (BC) (19/31.1%), and malignant adenomyoepitheliomas (19/31.1%). Intra- and peritumoral TILs, TANs, and TCD3⁺ and BCD79⁺ lymphocytes were counted, and based on the resulting median, the neoplasms were divided into low or high cell infiltration. BCs had the lowest density of intratumoral TILs (p = 0.02), and luminal B neoplasms showed a significantly higher density of intratumoral TCD3⁺ than luminal A cases. Neoplasms with a higher density of peritumoral CD3⁺ and CD79⁺ had significantly greater proliferative activity. High infiltration of intratumoral BCD79⁺ lymphocytes was related to nodal metastasis (p = 0.03). Intratumoral TILs and TCD3⁺ were associated with shorter survival time. Therefore, intratumoral lymphocyte infiltration is possibly an important feature in the progression of cancer and influences the survival in bitches with solid arrangement neoplasms. Full article

Colorectal cancer (CRC) is often associated with metastasis and recurrence and is the leading cause of cancer-related mortality. In the progression of CRC, recent studies have highlighted the critical role of neutrophils, particularly tumor-associated neutrophils (TANs). TANs have both tumor-promoting and tumor-suppressing activities, contributing to metastasis, immunosuppression, angiogenesis, and epithelial-to-mesenchymal transition. Tumor-promoting TANs promote tumor growth by releasing proteases, reactive oxygen species, and cytokines, whereas tumor-suppressing TANs enhance immune responses by activating T cells and natural killer cells. Understanding the mechanisms underlying TAN mobilization, plasticity, and their role in the tumor microenvironment has revealed potential therapeutic targets. This review provides a comprehensive overview of TAN biology in CRC and discusses both the tumor-promoting and tumor-suppressing functions of neutrophils. Novel therapeutic approaches targeting TANs, such as chemokine receptor antagonists, aim to modulate neutrophil reprogramming and offer promising avenues for improving treatment outcomes of CRC. Full article

The characteristics of neutrophils play a crucial role in defining the tumor inflammatory environment. However, the function of tumor-associated neutrophils (TANs) in tumor immunity and their response to immune checkpoint inhibitors (ICIs) remains incompletely understood. By analyzing single-cell RNA sequencing data from over 600,000 cells in gastric cancer (GSE163558 and GSE183904), colorectal cancer (GSE205506), and lung cancer (GSE207422), we identified neutrophil subsets in primary gastric cancer that are associated with the treatment response to ICIs. Specifically, we focused on neutrophils with high expression of CD44 (CD44_NEU), which are abundant during tumor progression and exert significant influence on the gastric cancer immune microenvironment. Machine learning analysis revealed 22 core genes associated with CD44_NEU, impacting inflammation, proliferation, migration, and oxidative stress. In addition, multiple immunofluorescence staining and gastric cancer spatial transcriptome data (GSE203612) showed a correlation between CD44_NEU and T-cell infiltration in gastric cancer tissues. A risk score model derived from seven essential genes (AQP9, BASP1, BCL2A1, PLEK, PDE4B, PROK2, and ACSL1) showed better predictive capability for patient survival compared to clinical features alone, and integrating these scores with clinical variables resulted in a prognostic nomogram. Overall, this study highlights the heterogeneity of TANs, particularly the CD44_NEU critical influence on immunotherapy outcomes, paving the way for personalized treatment strategies. Full article

Background: Tumor-associated neutrophils (TANs) are important modulators of the tumor microenvironment with opposing functions that can promote and inhibit tumor progression. The prognostic role of TANs in early luminal breast cancer is unclear. Methods: A total of 144 patients were treated for early-stage hormone-receptor-positive breast cancer as part of an Accelerated Partial Breast Irradiation (APBI) phase II trial. Resection samples from multiple locations were processed into tissue microarrays and sections thereof immunohistochemically stained for CD66b+ neutrophils. CD66b+ neutrophil density was measured separately in the stromal and intraepithelial compartment. Results: High stromal and intraepithelial CD66b+ TAN density was a negative prognostic factor in central tumor samples. In addition, neutrophil density in adjacent normal breast tissue and lymph node samples also correlated with reduced disease-free survival. TAN density correlated with CD163+ M2-like tumor-associated macrophage (TAM) density, which we analyzed in a previous study. TANs were a negative prognostic factor in tumors with an elevated M1/M2 TAM ratio, while this impact on patient outcome was lost in tumors with a low M1/M2 ratio. A combined multivariate analysis of TAM and TAN density revealed that only TAM polarization status was an independent prognostic factor. Conclusions: CD66b+ neutrophils were a negative prognostic factor in early-stage luminal breast cancer in single-marker analysis. Combined analysis with TAMs could be necessary to correctly evaluate their prognostic impact in future studies. TAN recruitment might act as a compensatory mechanism of immunoevasion and disease progression in tumors that are unable to sufficiently attract and polarize TAMs. Full article

Lung cancer is the most common cause of cancer-related death in both males and females in the U.S. and non-small-cell lung cancer (NSCLC) accounts for 85%. Although the use of first- or second-line immune checkpoint inhibitors (ICIs) exhibits remarkable clinical benefits, resistance to ICIs develops over time and dampens the efficacy of ICIs in patients. Tumor-associated neutrophils (TANs) have an important role in modulating the tumor microenvironment (TME) and tumor immune response. The major challenge in the field is to characterize the TANs in NSCLC TME and understand the link between TAN-related immunosuppression with ICI treatment response. In this review, we summarize the current studies of neutrophil interaction with malignant cells, T-cells, and other components in the TME. Ongoing clinical trials are aimed at utilizing reagents that have putative effects on tumor-associated neutrophils, in combination with ICI. Elevated neutrophil populations and neutrophil-associated factors could be potential therapeutic targets to enhance anti-PD1 treatment in NSCLC. Full article

TIICs are critical components of the TME and are used to estimate prognostic and treatment responses in many malignancies. TIICs in the tumor microenvironment are assessed and quantified by categorizing immune cells into three subtypes: CD66b+ tumor-associated neutrophils (TANs), FoxP3+ regulatory T cells (Tregs), and CD163+ tumor-associated macrophages (TAMs). In addition, many cancers have tumor-infiltrating M1 and M2 macrophages, neutrophils (Neu), CD4+ T cells (T-helper), CD8+ T cells (T-cytotoxic), eosinophils, and mast cells. A variety of clinical treatments have linked tumor immune cell infiltration (ICI) to immunotherapy receptivity and prognosis. To improve the therapeutic effectiveness of immune-modulating drugs in a wider cancer patient population, immune cells and their interactions in the TME must be better understood. This study examines the clinicopathological effects of TIICs in overcoming tumor-mediated immunosuppression to boost antitumor immune responses and improve cancer prognosis. We successfully analyzed the predictive and prognostic usefulness of TIICs alongside TMB and ICI scores to identify cancer’s varied immune landscapes. Traditionally, immune cell infiltration was quantified using flow cytometry, immunohistochemistry, gene set enrichment analysis (GSEA), CIBERSORT, ESTIMATE, and other platforms that use integrated immune gene sets from previously published studies. We have also thoroughly examined traditional limitations and newly created unsupervised clustering and deconvolution techniques (SpatialVizScore and ProTICS). These methods predict patient outcomes and treatment responses better. These models may also identify individuals who may benefit more from adjuvant or neoadjuvant treatment. Overall, we think that the significant contribution of TIICs in cancer will greatly benefit postoperative follow-up, therapy, interventions, and informed choices on customized cancer medicines. Full article

High-risk human papillomavirus (HPV) infection is one of the leading causes of oropharyngeal squamous cell carcinoma (OPSCC), while the correlation between HPV and oral squamous cell carcinoma (OSCC) remains controversial. The inflammatory infiltrate involved in these epithelial neoplasms differs based on their association with HPV. HPV− tumors show higher tumor-associated neutrophil (TAN) infiltration. It is believed that TANs can play a dual role in cancer by exerting either anti-tumorigenic or pro-tumorigenic effects. However, the impact of HPV status on neutrophil polarization remains unknown. Therefore, this study aimed to investigate the effect of OSCC cells, both HPV− and HPV16+, on the functional phenotype of neutrophils. Peripheral blood neutrophils were stimulated with supernatants from OSCC cell lines and non-tumorigenic HaCaT keratinocytes transduced with HPV16 E6/E7 oncogenes. Subsequently, cytokine production, cell viability, metabolism, expression of degranulation markers, and PD-L1 expression were evaluated. Our findings demonstrate that in contrast to UPCI:SCC154 (HPV+ OSCC) cells, the SCC-9 (HPV− OSCC) cell line induced a highly activated functional state in neutrophils, which is potentially associated with a pro-tumorigenic effect. The HaCaT 16-E7 supernatant only stimulated the activation of some neutrophil functions. Understanding the complex interplay between neutrophils and their microenvironment has the potential to identify TANs as viable therapeutic targets. Full article

One area of cancer research is the interaction between cancer cells and immune cells, in which chemokines play a vital role. Despite this, a comprehensive summary of the involvement of C-X-C motif ligand 1 (CXCL1) chemokine (also known as growth-regulated gene-α (GRO-α), melanoma growth-stimulatory activity (MGSA)) in cancer processes is lacking. To address this gap, this review provides a detailed analysis of CXCL1’s role in gastrointestinal cancers, including head and neck cancer, esophageal cancer, gastric cancer, liver cancer (hepatocellular carcinoma (HCC)), cholangiocarcinoma, pancreatic cancer (pancreatic ductal adenocarcinoma), and colorectal cancer (colon cancer and rectal cancer). This paper presents the impact of CXCL1 on various molecular cancer processes, such as cancer cell proliferation, migration, and invasion, lymph node metastasis, angiogenesis, recruitment to the tumor microenvironment, and its effect on immune system cells, such as tumor-associated neutrophils (TAN), regulatory T (T_reg) cells, myeloid-derived suppressor cells (MDSCs), and macrophages. Furthermore, this review discusses the association of CXCL1 with clinical aspects of gastrointestinal cancers, including its correlation with tumor size, cancer grade, tumor–node–metastasis (TNM) stage, and patient prognosis. This paper concludes by exploring CXCL1’s potential as a therapeutic target in anticancer therapy. Full article

Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide and the fourth leading cause of cancer-related death globally. Tumor cells recruit and remodel various types of stromal and inflammatory cells to form a tumor microenvironment (TME), which encompasses cellular and molecular entities, including cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs), immune cells, myeloid-derived suppressor cells (MDSCs), immune checkpoint molecules and cytokines that promote cancer cell growth, as well as their drug resistance. HCC usually arises in the context of cirrhosis, which is always associated with an enrichment of activated fibroblasts that are owed to chronic inflammation. CAFs are a major component of the TME, providing physical support in it and secreting various proteins, such as extracellular matrices (ECMs), hepatocyte growth factor (HGF), insulin-like growth factor 1/2 (ILGF1/2) and cytokines that can modulate tumor growth and survival. As such, CAF-derived signaling may increase the pool of resistant cells, thus reducing the duration of clinical responses and increasing the degree of heterogeneity within tumors. Although CAFs are often implicated to be associated with tumor growth, metastasis and drug resistance, several studies have reported that CAFs have significant phenotypic and functional heterogeneity, and some CAFs display antitumor and drug-sensitizing properties. Multiple studies have highlighted the relevance of crosstalk between HCC cells, CAFs and other stromal cells in influence of HCC progression. Although basic and clinical studies partially revealed the emerging roles of CAFs in immunotherapy resistance and immune evasion, a better understanding of the unique functions of CAFs in HCC progression will contribute to development of more effective molecular-targeted drugs. In this review article, molecular mechanisms involved in crosstalk between CAFs, HCC cells and other stromal cells, as well as the effects of CAFs on HCC-cell growth, metastasis, drug resistance and clinical outcomes, are comprehensively discussed. Full article

Breast cancer (BC) is well-known for being a leading cause of death worldwide. It is classified molecularly into luminal A, luminal B HER2−, luminal B HER2+, HER2+, and triple-negative breast cancer (TNBC). These subtypes differ in their prognosis; thus, understanding the tumor microenvironment (TME) makes new treatment strategies possible. The TME contains populations that exhibit anti-tumorigenic actions such as tumor-associated eosinophils. Moreover, it contains pro-tumorigenic populations such as tumor-associated neutrophils (TANs), or monocyte-derived populations. The monocyte-derived populations are tumor-associated macrophages (TAMs) and MDSCs. Thus, a monocyte can be considered a maestro within the TME. Moreover, the expansion of monocytes in the TME depends on many factors such as the BC stage, the presence of macrophage colony-stimulating factor (M-CSF), and the presence of some chemoattractants. After expansion, monocytes can differentiate into pro-inflammatory populations such as M1 macrophages or anti-inflammatory populations such as M2 macrophages according to the nature of cytokines present in the TME. Differentiation to TAMs depends on various factors such as the BC subtype, the presence of anti-inflammatory cytokines, and epigenetic factors. Furthermore, TAMs and MDSCs not only have a role in tumor progression but also are key players in metastasis. Thus, understanding the monocytes further can introduce new target therapies. Full article