Research ArticleExperimental Studies
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Inhibition of Cholesterol Transport from Lysosomes by Itraconazole Repolarizes Tumor-associated Macrophages to Anti-tumor M1 type

YUMI TAKIMOTO, HIROSHI TSUBAMOTO, YUSHI TSUBAMOTO, ATSUSHI TAMURA, ROZE TANIGUCHI, KAZUKO SAKATA, TOMOKO UEDA, SACHIYO NARITA, YU WAKIMOTO and SEIJI MABUCHI
Anticancer Research December 2025, 45 (12) 5255-5266; DOI: https://doi.org/10.21873/anticanres.17866

Abstract

Background/Aim: Targeting tumor-associated macrophages (TAMs) represents a promising strategy for next-generation immunotherapy. This study investigates the underlying mechanisms of TAM repolarization from the pro-tumorigenic M2 phenotype to the anti-tumorigenic M1 phenotype induced by itraconazole (ITZ).

Materials and Methods: M2 macrophages derived from THP-1 cells were used in all experiments, and ITZ was administered at a concentration of 10−5 M. Morphological changes were monitored via time-lapse imaging. Single-cell RNA sequencing (scRNA-seq) and triple-color immunostaining for organelles, cholesterol, and the M1 marker interleukin (IL)-1β were performed with and without ITZ treatment. For inhibition studies, β-cyclodextrin polyrotaxane (βCD-PRX), a compound that removes cholesterol from lysosomes, was used. The effects were assessed by time-lapse imaging and western blot analysis of the M2 marker CD163.

Results: Following ITZ treatment, a subpopulation of M2 macrophages exhibited morphological changes, shedding dendrites and migrating, indicative of an M1-like phenotype. Additionally, intracellular lipid droplets enlarged and swelled. scRNA-seq analysis revealed that M2 macrophages with reduced lysosomal vesicle biogenesis transitioned to an M1-like phenotype and identified 1,142 significantly enriched pathways, including M1-related signaling activation and cholesterol metabolism and transport pathways. Immunofluorescence analysis confirmed that macrophages shifting toward an M1-like phenotype expressed IL-1β, with enlarged intracellular lipid droplets identified as cholesterol-containing lysosomes. Notably, M2 macrophages that had adopted an M1-like morphology in response to ITZ reverted to their original M2-like shape and exhibited increased CD163 expression following βCD-PRX treatment.

Conclusion: Inhibition of lysosomal cholesterol release by ITZ reprogrammed M2 macrophages into an M1-like phenotype, revealing a novel mechanism that may serve as a foundation for developing innovative TAM-targeted immunotherapies.

Keywords:

Introduction

Tumor-associated macrophages (TAMs), key components of the TME, are typically classified into M1 and M2 subtypes. While M1 macrophages exhibit anti-cancer properties by expressing CD86 and Toll-like receptor 4 (TLR4) and secreting pro-inflammatory cytokines such as IL-6 and tumor necrosis factor-alpha (TNF-α), M2 macrophages promote tumor growth, invasion, angiogenesis, and immune tolerance through the secretion of IL-10 and transforming growth factor-beta (TGF-β). Tumors predominantly contain M2 macrophages, making them attractive targets for cancer therapy. Although multiple clinical trials targeting TAMs have been conducted, most demonstrated modest efficacy or were associated with significant toxicity, highlighting the need for more effective and safer therapeutic approaches (1).

Itraconazole (ITZ) is a well-known antifungal agent which inhibits ergosterol synthesis in the fungal membrane. ITZ has also demonstrated anticancer activity by inhibiting various signaling pathways, depending on the specific cancer cell types used in experimental studies (2). Several clinical trials have shown the benefits of ITZ administration. However, because the patent has expired, the clinical development of ITZ itself as an anticancer drug is limited. Consequently, drug repurposing efforts often aim to elucidate its mechanisms of action as a bridge to new drug discovery.

Previously, we demonstrated that ITZ repolarized M2-like TAMs into M1-like TAMs using leukemia-derived THP-1 cells, a widely accepted model mimicking TAMs within the TME (3). However, the mechanism was not elucidated, as THP-1-derived TAMs had heterogeneity, and only a subset of cells underwent repolarization from the M2 to the M1 phenotype. We investigated the repolarization mechanism at the single cell level mainly by immunofluorescence and single cell RNA sequencing (scRNAseq).

Materials and Methods

Cell culture and macrophage polarization. Human THP-1 monocytes were obtained from NIHS (JCRB Cell Bank, Osaka, Japan). THP-1 derived macrophages were maintained in Roswell Park Memorial Institute-1640 medium (Gibco BRL, Grand Island, NY, USA) containing 10% heat-inactivated fetal calf serum (GE Healthcare Life Sciences, Logan, UT, USA). All the cells were incubated at 37°C, in a humidified atmosphere with 5% CO2. The culture medium was designated as control medium (CM). M1 and M2 macrophages were established as previously described (4) by differentiating THP-1 monocytes into M0 macrophages, by means of a 24-h incubation with 100 nM phorbol 12-myristate 13-acetate (P8139; Sigma-Aldrich, St. Louis, MO, USA), followed by a 24-h incubation in CM. To obtain M1 macrophages, the M0 macrophages were polarized by means of a 48-h incubation with 20 ng/ml interferon gamma (IFN-γ; 285-IF; R&D Systems, Minneapolis, MN, USA) and 10 pg/ml of lipopolysaccharide (2630; Sigma-Aldrich), followed by a 24-h incubation in CM. M2 polarization was carried out by means of a 48-h incubation with 20 ng/ml IL-4 (204-IL; R&D Systems) and 20 ng/ml IL-13 (213-ILB; R&D Systems), followed by a 48-h incubation in CM.

Time-lapse imaging. THP-1 cells were plated to glass base dish (3910-035, IWAKI, Tokyo, Japan) at the concentration of 5×105 cells/dish and induced to M2 macrophages. Three days after induction to M2 macrophages, 1×10−5 M ITZ, dissolved in N,N-dimethylformamide (DMF), was added to the dishes. Observation with a fluorescent inverted microscope (TiE, Nikon, Tokyo, Japan) was started at the same time as ITZ addition, and time-lapse images were taken every 10 min for 48 h using NIS-Elements software (Nikon). The morphological assessment of M1 and M2 macrophages was performed according to a previous report, which demonstrated that M1 macrophages adopt an elongated shape with a dense cortical actin network, whereas M2 macrophages are more spherical with randomly distributed actin (5).

Single cell RNA sequencing with surface antigen labeling. M2 macrophages, treated with or without itraconazole (10−5 M) for 24 h, were labeled with antibodies against the M1 markers CD86 and CD284 (TLR4) and the M2 markers CD204 and CD163 using a TotalSeq-C hashtag (BioLegend) for 30 min at 4°C. The cells were then washed twice using centrifugation at 500 g for 5 min at 4°C with phosphate-buffered saline (PBS) supplemented with 2% (vol/vol) BSA. Single cell RNA sequencing (scRNAseq) was performed in Genome Information Research Center in Osaka University. Briefly, single-cell suspensions were loaded onto a Chromium Controller (10× Genomics) using Chromium Next GEM Single Cell 5′ Library and Gel Bead Kit v2 (10× Genomics). M2 macrophages treated with and without itraconazole were recovered and counted to 10,567 and 6,770 cells, respectively. All preparation steps were performed according to the manufacturer’s specifications (10× Genomics). Libraries were sequenced using the NovaSeq6000 (Illumina) at a read length of 28×90 to achieve a minimum of 20,000 reads per cell for gene expression and 5,000 reads per cell for cell-surface protein. The raw and processed single-cell RNA sequencing data generated in this study have been deposited in the NCBI Sequence Read Archive (SRA) under BioProject accession number PRJNA1303381.

Data processing and quality control of scRNAseq. We analyzed the sequenced data using Scanpy (version 1.10.4) (6). Quality filtering was performed to exclude low-quality cells with <200 expressed genes, unique molecular identifiers (UMIs) >60,000 and >10% mitochondrial-derived UMI counts. To explore cellular relationships and analyze the trajectory of cellular changes in response to ITZ treatment, we utilized Partition-based Graph Abstraction (PAGA) (7). Pathway activity was estimated using AUCell (8) as implemented in the decoupler package (version 1.8.0) (9) along with REACTOME gene sets (10) downloaded via MSigDB (“c2.cp.reactome.v2024.1.Hs.symbols.gmt”) (11). Visualization and trajectory analysis were conducted according to Scanpy tutorials, and pathway analysis followed the Single-Cell Best Practices online resource (https://www.sc-best-practices.org/preamble.html) (12).

Triple-labeling immunofluorescence. To detect differences in intracellular localization of cholesterol due to macrophage polarity, IL-1β (blue), cholesterol (green) and organelle (red) were stained simultaneously. IL-1β was stained with IL-1 beta Polyclonal Antibody (#PA5-88078, Thermo Fisher Scientific, Waltham, MA, USA) for the primary antibody and Goat anti-Rabbit IgG (H+L) Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 405 (#A-31556, Thermo Fisher Scientific) for the secondary antibody, and cholesterol was stained with BODIPY480/508 cholesterol (24618, Cayman Chemical, Ann Arbor, MI, USA). Organelles were stained for endoplasmic reticulum (ER), lysosomes, and autophagosomes, using Alexa Fluor 647 Anti-KDEL Antibody (EPR12668), Alexa Fluor 647 Conjugated LAMP1 antibody and Alexa Fluor 647 Conjugate LC3B (D11) XP Rabbit mAb, respectively (Cell Signaling, Danvers, MA, USA). M2 macrophages were established as previously described. M2 macrophages were incubated with and without 1×10−5 M ITZ for 3days, and after that, they were incubated with BODIPY480/508 cholesterol. They were then fixed with 4% paraformaldehyde. Macrophages were permeabilized and blocked to prevent non-specific antibody binding. Macrophages were reacted with primary antibodies for 3 h and then with secondary antibodies, followed by overnight incubation at 4°C with antibodies for organelles.

All the antibodies were diluted by PBS containing 0.1% saponin and 2.5% normal horse serum. After 3 washes with PBS, mounting in VectaShield (VECTASHIELD Hardset Antifade Mounting Medium, Vector Laboratories, Inc., Newark, CA, USA) was performed according to the technical datasheet. Macrophages were analyzed by fluorescence imaging using 40× water immersion objective on Zeiss LSM780 confocal microscope driven by the ZEN 2009 software (Carl Zeiss).

Inhibition of ITZ using βCD-PRX. We used βCD-PRX modified with 2-(2-hydroxyethoxy)ethyl groups (number of threading βCD: 13.2, number-average molecular weight: 31,200) which facilitates the removal of cholesterol from lysosomes (13). It is a supramolecular structured polymer designed to release threading βCDs specifically in acidic lysosomes through the acid-induced degradation of βCD-PRX. After M2 macrophages were cultured with 10−5 M ITZ for 3 days, 1 mM βCD-PRX was added to the medium and time-lapse images were taken every 5 min for the first 24 h and every 10 min thereafter until the end of imaging at 48 h. On the third day after adding βCD-PRX, the macrophages were scraped, centrifuged, and washed with PBS. They were then lysed using the CelLytic M lysis buffer containing a protease inhibitor cocktail (all from Sigma-Aldrich). Proteins (2 μg) were size-fractionated by means of 5%–20% sodium dodecyl sulfate-polyacrylamide gel electrophoresis and transferred to a polyvinylidene difluoride membrane (ATTO, Tokyo, Japan), which was blocked with EzBlock Chemi (ATTO) and incubated with the primary antibodies, anti-CD163 (16646-1-AP; 1:1,000; Proteintech Japan, Tokyo, Japan) and anti-β-actin (1:1,000; MBL, Nagoya, Japan). After washing with PBS containing 0.01% Tween-20 (Wako Pure Chemical Industries, Osaka, Japan), we probed the blots with secondary antibodies for 1 h at room temperature. Immunoreactivity was visualized using an ECL Prime Western Blot Detection Kit (GE Healthcare Life Sciences, Little Chalfont, UK). Band intensity was quantified using ImageQuant™ LAS4010 and ImageQuant™ TL software (GE Healthcare Life Sciences). The relative intensity of the target protein band was normalized to that of the internal control (β-actin) for each sample.

Results

Time-lapse imaging. To observe morphological changes in M2 macrophages upon ITZ treatment, time-lapse imaging was performed. A subset of M2 macrophages showed M1-like morphological changes after the addition of ITZ, such as the appearance of dendrites and the start of migration. In addition, the cells that showed this change showed an increase in lipid droplet size and swelling (Figure 1).

Figure 1.
Figure 1.

The effect of ITZ on the polarity of TAMs. After administration of ITZ, we identified a subset of cells that changed from spherical M2 macrophages to an M1-like morphology with dendrites.

Single-cell RNA sequencing (scRNA-seq) analysis. To investigate transcriptomic changes following ITZ treatment, scRNA-seq analysis was performed. Newly emerging clusters after ITZ treatment exhibited co-expression of CD86 and CD284 (TLR4) along with their corresponding mRNAs. However, these markers were also expressed in pre-treatment clusters, indicating that the observed expression was not a specific change induced by ITZ. IL-1β was identified as a significantly up-regulated M1 marker. Among the 12 identified clusters, cluster C2 exhibited high IL-1β expression and comprised 87% of ITZ-treated cells. Trajectory inference analysis revealed that clusters C1 and C8, which predominantly consisted of untreated cells (92.9% and 72.3%, respectively), were identified as precursor clusters with the potential to transition into the M1-like cluster C2 following ITZ treatment (Figure 2). We then compared ITZ-treated cells in cluster C2 with untreated cells in clusters C1 and C8 and identified 1,142 significantly enriched pathways with an adjusted p-Value of less than 0.05. Treatment with ITZ activated M1-related signaling pathways, including interleukin-1, nuclear factor-kappa B (NF-κB), and tumor necrosis factor (TNF) (Table I). Pathways related to cholesterol metabolism and transport were also altered by ITZ treatment (Table II), and lysosomal vesicle biogenesis was more strongly inhibited in ITZ-treated cells than in untreated cells (Table II).

Figure 2.
Figure 2.

Single-cell RNA sequencing analysis of THP-1-derived M2 macrophages with or without itraconazole treatment. A: Clustering of the cells, B: Treatment with or without itraconazole (ITZ), C: mRNA expression of IL-1β, D: Trajectory analysis, E: mRNA expression of IL-1β, F: Pathway of lysosome vesicle biogenesis. Among the 12 identified clusters, cluster 2 exhibited high expression levels of IL-1β and comprised 87% of itraconazole (ITZ)-treated cells. Trajectory inference analysis indicated that cluster 2 was closely related to clusters 1 and 8, which predominantly consisted of untreated cells (92.9% and 72.3%, respectively). Single-cell RNA sequencing analysis suggested that, following ITZ treatment, a subpopulation of M2 macrophages with clusters 1 and 8 transitioned to an M1-like cluster 2 characterized by IL-1β expression. Furthermore, the lysosomal vesicle biogenesis pathway was suppressed in clusters 1, 2, and 8. Normalized gene expression levels are shown for mRNA expression. For pathway activity, AUC scores calculated using AUCell are shown, where larger values suggest higher pathway activity.

View this table:
Table I.

Altered pathways related to M1 and M2 phenotypes following ITZ treatment.

View this table:
Table II.

Effects of ITZ treatment on cholesterol pathways.

Triple-labeling immunofluorescence analysis. To investigate intracellular cholesterol localization changes due to macrophage polarity, a triple-labeling immunofluorescence study was conducted. In M2 macrophages, free cholesterol was widely present in the cytoplasm and drops of esterified cholesterol were not noticeable. However, after ITZ treatment, the intracellular concentration of Il-1β increased, and lysosomal swelling and accumulation of cholesterol in lysosomes became more pronounced (Figure 3).

Figure 3.
Figure 3.

Effect of itraconazole on lysosomal cholesterol accumulation in M2 macrophages. ITZ-treated M2 macrophages exhibited enlarged lysosomes, cholesterol accumulation, and IL-1β expression. M2 macrophages were incubated with 1×10−5 M itraconazole (ITZ) for 72 h and stained with LAMP1 (lysosomes, red; A), BODIPY (cholesterol ester and free cholesterol, green; B), and IL-1β (M1 marker, blue; C). (D) Merged confocal images. White arrowhead, colocalization of LAMP1 and cholesterol; solid arrow, cholesterol; open arrow, LAMP1.

Effects of βCD-PRX on ITZ-treated M2 macrophages. To assess the effects of cholesterol accumulation, ITZ-treated M2 macrophages were treated with βCD-PRX, and time-lapse imaging and western blot analysis were performed. M2 macrophages treated with ITZ in the M1-like morphology began to shorten their dendrites 1 h after addition of βCD-PRX. After 10 h, they began to shift toward a spherical shape and returned to a spherical M2-like morphology at 24 h. This M2-like morphology was maintained until the end of the 48-h observation period (Figure 4). Western blots showed that CD163, a surface-expressed marker protein of M2 macrophages, is down-regulated after ITZ treatment. However, after βCD-PRX was added under continuous ITZ administration, CD163 expression increased to the same level as that of M2 macrophages (Figure 5).

Figure 4.
Figure 4.

The effect of βCD-PRX on the morphological changes of M2 macrophages repolarized to an M1-like phenotype by ITZ treatment. Morphological changes in ITZ-treated M2 macrophages with an M1-like shape were examined after the addition of 1 mM βCD-PRX under continuous 10−5 M ITZ treatment. ITZ-added M2 macrophage (hollow arrow) began to shorten their dendrites 1 hr after addition of βCD-PRX, and returned to a spherical M2-like morphology at 24 hr. This M2-like morphology was maintained until the end of the 48-hour observation. βCD-PRX; 2-(2-hydroxyethoxy)ethyl (HEE) carbamate-modified β-CD/Pluronic-based polyrotaxane.

Figure 5.
Figure 5.

The effect of βCD-PRX on the expression of CD163, a surface marker of M2 macrophages, repolarized to an M1-like phenotype by ITZ treatment. M2 macrophages were induced from THP-1 cells (A); M2 macrophages were cultured with ITZ for 72 h (B) and then 1 mM βCD-PRX was added under continuous ITZ administration (C). Quantitative analysis of CD163/β-actin expression derived from western blot results is shown. trCD163, a surface-expressed marker protein of M2 macrophages, is downregulated after ITZ treatment. However, after βCD-PRX was added under continuous ITZ administration, CD163 expression increased to the same level as that of M2 macrophages. βCD-PRX; 2-(2-hydroxyethoxy)ethyl (HEE) carbamate-modified β-CD/Pluronic-based polyrotaxane.

Discussion

Cholesterol homeostasis plays a pivotal role in the TME and has garnered increasing attention as a potential target for cancer therapy (14). This study demonstrates that ITZ promotes the repolarization of M2 macrophages into the M1 phenotype by inhibiting cholesterol efflux from lysosomes. A subpopulation of M2 macrophages with reduced lysosomal vesicle biogenesis transitioned to an M1-like phenotype following ITZ treatment. Notably, depletion of lysosomal cholesterol using βCD-PRX induced macrophages that had undergone M1 polarization to revert to their original M2 phenotype, highlighting the reversibility of this process. This novel finding reveals a previously unreported mechanism by which ITZ modulates TAM repolarization through the regulation of lysosomal cholesterol release.

Compared with M1 macrophages, M2 TAMs exhibit elevated cholesterol levels, which are transferred to cancer cells via cholesterol-rich lipid rafts or direct cell-to-cell contact. This cholesterol transfer promotes cancer cell growth and survival (15). The maintenance of the M2 TAM phenotype relies on a continuous supply of cholesterol to the extracellular environment. The knockout of ATP-binding cassette (ABC) transporters ABCA1 and ABCG1, which mediate cholesterol efflux, induces TAM polarization toward a tumoricidal M1-like phenotype (16).

The accumulation of cholesterol in lysosomes and the repolarization of tumor-associated macrophages (TAMs) have been reported in treatments involving acidophilic compounds similar to itraconazole (ITZ). Chloroquine (CQ), an acidophilic antimalarial drug, has been extensively studied for its roles in autophagy regulation and cancer therapy (17). CQ accumulates in acidified intracellular compartments, such as endosomes and lysosomes, increasing their pH and leading to lysosomal dysfunction. This disruption induces the repolarization of M2 TAMs into the M1 phenotype.

The effects of ITZ on lysosomes have been reported in studies using human umbilical vein endothelial cells (HUVECs) and epithelial ovarian cancer (EOC) cells, where ITZ inhibited cell proliferation. In HUVECs, ITZ was reported to bind to Niemann-Pick C1 (NPC1), a lysosomal membrane protein, and disrupts intracellular cholesterol trafficking (18). Consistent with this, triazoles including ITZ have also been shown to inhibit cholesterol export from lysosomes by binding to NPC1 (19). Lysosomal cholesterol accumulation inhibited mechanistic target of rapamycin (mTOR) signaling, leading to HUVEC growth inhibition. Pathway analysis of EOC cells revealed that ITZ modulated pathways related to vesicular trafficking and the dynamics of the trans-Golgi network and late endosomal/lysosomal compartments. Although the molecular mechanism of ITZ in EOC cells remains unclear, knockout of vacuolar protein sorting-associated protein 54 (VPS54) and C18orf8 – both implicated in lysosomal biology and dynamics – enhanced lysosomal cholesterol accumulation and swelling, thereby potentiating ITZ’s effects. ITZ showed synergistic effects with CQ in vitro, however, a clinical trial involving 11 patients with platinum-resistant or refractory EOC observed no objective responses to ITZ in combination with CQ (20). This contrasts with another study where ITZ demonstrated clinical benefits when combined with chemotherapy (21), suggesting that ITZ and CQ together may not fully exploit ITZ’s diverse anticancer effects on both cancer cells and the TME. Other innovative approaches, such as inflammation-triggering engineered macrophages (‘MacTriggers’), have also demonstrated the therapeutic potential of targeting TAMs in chemoresistant tumors (22). Moreover, cholesterol efflux from C1QB-expressing TAMs has recently been associated with resistance to CAR-T cell therapy (23), highlighting that macrophage cholesterol metabolism may broadly influence the efficacy of cancer immunotherapies.

Study limitations. Firstly, this study did not identify the precise mechanism of cholesterol accumulation in lysosomes in THP-1-derived macrophages. It remains unclear in this study whether the accumulation in lysosomes is due to acidophilic properties of ITZ, the impairment of release from lysosomes caused by NPC-1 binding, or the involvement of other specific binding molecules. Understanding these mechanisms is crucial for the development of more effective anticancer therapies. Secondly, the experimental concentration of itraconazole (10 μM) is slightly higher than clinically observed serum levels (~1–2 μM); however, it remains within an acceptable range for in vitro studies and is consistent with prior reports (24). Finally, the applicability of these in vitro findings to cancer tissues in patients remains uncertain. Further investigation using patient-derived cancer tissues before and after ITZ treatment is essential to validate the relevance of these findings in a clinical setting. Notably, the Window of Opportunity clinical trial (jRCTs051190006) is currently ongoing to address these questions. Despite these limitations, the discovery that inhibition of lysosomal cholesterol release induces M2-to-M1 macrophage repolarization represents a significant step forward in developing therapies targeting cholesterol metabolism within the TME.

Conclusion

Single-cell RNA sequencing and multicolor immunofluorescence analyses demonstrated that lysosomal cholesterol accumulation reprograms M2 macrophages toward an M1-like phenotype, whereas depletion of lysosomal cholesterol by βCD-PRX restores the M2 phenotype. These findings suggest that modulation of lysosomal cholesterol could be a promising strategy for developing novel TAM-targeted immunotherapies.

Acknowledgements

This work was supported by Hyogo Medical University Grant for Research Promotion, 2024.

Footnotes

  • Authors’ Contributions

    HT conceived and designed the study. YTki performed most of the experiments. KS, AT, and RT contributed to the experiments. YTki analyzed the data with support from YTsu. YTki drafted the manuscript. TU, SN, YW, and SM contributed mainly to manuscript revision and editing. All Authors read and approved the final manuscript.

  • Supplementary Material

    Supplementary Video 1: Time-lapse imaging corresponding to Figure 1. DOI: 10.6084/m9.figshare.29820008; Supplementary Video 2: Time-lapse imaging corresponding to Figure 4. DOI: 10.6084/m9.figshare.29820155

  • Conflicts of Interest

    The Authors declare no conflicts of interest in relation to this study.

  • Artificial Intelligence (AI) Disclosure

    No artificial intelligence (AI) tools, including large language models or machine learning software, were used in the preparation, analysis, or presentation of this manuscript.

  • Received May 12, 2025.
  • Revision received September 11, 2025.
  • Accepted September 17, 2025.

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Inhibition of Cholesterol Transport from Lysosomes by Itraconazole Repolarizes Tumor-associated Macrophages to Anti-tumor M1 type
YUMI TAKIMOTO, HIROSHI TSUBAMOTO, YUSHI TSUBAMOTO, ATSUSHI TAMURA, ROZE TANIGUCHI, KAZUKO SAKATA, TOMOKO UEDA, SACHIYO NARITA, YU WAKIMOTO, SEIJI MABUCHI
Anticancer Research Dec 2025, 45 (12) 5255-5266; DOI: 10.21873/anticanres.17866
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