Macrophages are immune cells belonging to the mononuclear phagocyte system. They play crucial roles in immune defense, surveillance, and homeostasis. This review systematically discusses the types of hematopoietic progenitors that give rise to macrophages, including primitive hematopoietic progenitors, erythro-myeloid progenitors, and hematopoietic stem cells. These progenitors have distinct genetic backgrounds and developmental processes. Accordingly, macrophages exhibit complex and diverse functions in the body, including phagocytosis and clearance of cellular debris, antigen presentation, and immune response, regulation of inflammation and cytokine production, tissue remodeling and repair, and multi-level regulatory signaling pathways/crosstalk involved in homeostasis and physiology. Besides, tumor-associated macrophages are a key component of the TME, exhibiting both anti-tumor and pro-tumor properties. Furthermore, the functional status of macrophages is closely linked to the development of various diseases, including cancer, autoimmune disorders, cardiovascular disease, neurodegenerative diseases, metabolic conditions, and trauma. Targeting macrophages has emerged as a promising therapeutic strategy in these contexts. Clinical trials of macrophage-based targeted drugs, macrophage-based immunotherapies, and nanoparticle-based therapy were comprehensively summarized. Potential challenges and future directions in targeting macrophages have also been discussed. Overall, our review highlights the significance of this versatile immune cell in human health and disease, which is expected to inform future research and clinical practice.

Introduction: Pentraxin 3 (PTX3) is an essential regulator of the immune system. However, the immune‐modulatory role of PTX3 in the tumor microenvironment of glioma has not been elucidated.Methods: The RNA seq samples were obtained from The Cancer Genome Atlas (TCGA) and the China Glioma Genome Atlas (CGGA) datasets. The single‐cell sequencing data of glioblastoma (GBM) samples were obtained from the Single Cell Portal platform (http://singlecell.broadinstitute.org). Immunohistochemistry was used to assess PTX3 expression, HAVCR2, PD‐1, PD‐L1, and CD276 in glioma sections from the Xiangya cohort (n = 60). Multiplex immunofluorescence staining of PTX3, CD68, and CD163 was performed in several solid cancer types, including GBM. HMC3 was cocultured with U251 and U87, and transwell assay and flow cytometry assay were performed to explore the migration and polarization activity of HMC3.Results: PTX3 expression is significantly increased in GBM. PTX3 expression predicts worse survival in the Xiangya cohort. PTX3 is closely related to the expression of PD‐1, PD‐L1, CD276, and HAVCR2 in the tumor microenvironment. Additionally, PTX3 is involved in tumorigenic and immunogenic processes, especially the activity of macrophages based on various signaling pathways in cellular communications and critical transcription factors. Specifically, PTX3 actively mediates macrophages' infiltration, migration, and inflammation‐resolving‐polarization. PTX3 could also predict immunotherapy response.Conclusion: PTX3 is critically involved in macrophage infiltration, migration, and inflammation‐resolving‐polarization and modulates an immunosuppressive microenvironment.

The tumor microenvironment (TME) represents a metabolic battleground where immune cells and cancer cells vie for essential nutrients, ultimately influencing antitumor immunity and treatment outcomes. Recent advancements have shed light on how the metabolic reprogramming of immune cells, including macrophages, T cells, and DCs, determines their functional polarization, survival, and interactions within the TME. Factors such as hypoxia, acidosis, and nutrient deprivation drive immune cells toward immunosuppressive phenotypes, while metabolic interactions between tumors and stromal cells further entrench therapeutic resistance. This review synthesizes new insights into the metabolic checkpoints that regulate immune cell behavior, focusing on processes like glycolysis, oxidative phosphorylation (OXPHOS), lipid oxidation, and amino acid dependencies. We emphasize how metabolic enzymes (e.g., IDO1, ACLY, CPT1A) and metabolites (e.g., lactate, kynurenine) facilitate immune evasion, and we propose strategies to reverse these pathways. Innovations such as single-cell metabolomics, spatial profiling, and AI-driven drug discovery are transforming our understanding of metabolic heterogeneity and its clinical implications. Furthermore, we discuss cutting-edge therapeutic approaches—from dual-targeting metabolic inhibitors to biomaterial-based delivery systems—that aim to reprogram immune cell metabolism and enhance the effectiveness of immunotherapy. Despite the promise in preclinical studies, challenges persist in translating these findings to clinical applications, including biomarker validation, metabolic plasticity, and interpatient variability. By connecting mechanistic discoveries with translational applications, this review highlights the potential of immunometabolic targeting to overcome resistance and redefine precision oncology.

CD147 plays an important role in promoting tumor proliferation and inhibiting cancer cell apoptosis in the tumor microenvironment. However, the mechanisms by which CD147 is involved in tumorigenesis remains unclear. This study systematically analyzed the prognostic value and immune characteristics of CD147 in 31 cancer types. The expression levels and mutant landscapes of CD147 in pan-cancer were explored. The Kaplan-Meier (KM) analysis was applied to analyze the prognostic value of CD147. The immune characteristics of CD147 in the tumor microenvironment were evaluated via TIMER 2.0 and R package (immunedeconv). We also explored the expression of CD147 on tumor cells and stromal cells through Gene Set Variation Analysis and single-cell sequencing analysis. The co-expression of CD147 and macrophage markers CD68 and CD163 in pan-cancer was detected using multiplex immunofluorescence staining on tissue microarrays. CD147 was found to be overexpressed in almost all cancer types, which was related to poor outcome. CD147 expression exhibited a strong association with immune infiltrates, immune checkpoint molecules, and neoantigen levels in the tumor microenvironment. In addition, CD147 was expressed on various cell types in the tumor microenvironment, including tumor cells, macrophages, T cells, monocytes, fibroblasts, etc. Furthermore, multiplex immunofluorescence revealed the co-expression pattern of CD147 and macrophage markers CD68 and CD163 in many tumor types. Finally, the immunotherapy response and sensitive small molecule drugs based on CD147 expression were predicted. In sum, CD147 has a significant relationship with the clinical outcome and immune infiltrates in multiple cancer types. Inhibiting the CD147-dependent signaling pathways might be a promising therapeutic strategy for tumor immunotherapy.

Gliomas are primary malignant brain tumors. Monocytes have been proved to actively participate in tumor growth. Weighted gene co-expression network analysis was used to identify meaningful monocyte-related genes for clustering. Neural network and SVM were applied for validating clustering results. Somatic mutation and copy number variation were used for defining the features of identified clusters. Differentially expressed genes (DEGs) between the stratified groups after performing elastic regression and principal component analyses were used for the construction of risk scores. Monocytes were associated with glioma patients’ survival and exhibited high predictive value. The prognostic value of risk score in glioma was validated by the abundant expression of immune checkpoint and metabolic profile. Additionally, high risk score was positively associated with the expression of immunogenic and antigen presenting factors, which indicated high immune infiltration. A prognostic model based on risk score demonstrated high accuracy rate of receiver operating characteristic curves. Compared with previous studies, our research dissected functional roles of monocytes from large-scale analysis. Findings of our analyses strongly support an immune modulatory and prognostic role of monocytes in glioma progression. Notably, monocyte could be an effective predictor for therapy responses of glioma patients.