5-Aminolevulinic Acid photodynamic therapy treats HPV-associated diseases by promoting M1 macrophage polarization through STEAP3/p53/SLC7A11-mediated ferroptosis

IF 2.7 3区医学 Q2 ONCOLOGY

Photodiagnosis and Photodynamic Therapy Pub Date : 2026-06-01 Epub Date: 2026-05-22 DOI:10.1016/j.pdpdt.2026.105523

Rui Xu , Aijia Ding , Bichun Xu , Jing Shen , Junpeng Li , Hui Liu , Yuan Deng , Youfan Zhang , Yue Zheng , Kang Zeng

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Abstract

Background

Human papillomavirus (HPV) infection is a major driver of various malignancies, accounting for approximately 90% of cervical cancer cases and 70% of oropharyngeal cancer cases worldwide, yet therapies for persistent lesions remain limited. 5-aminolevulinic acid photodynamic therapy (ALA-PDT) eliminates HPV-infected cells via reactive oxygen species (ROS)-mediated apoptosis and immune modulation, but its immune regulatory mechanisms remain undefined.

Methods

Macrophage polarization and ferroptosis were characterized through quantitative polymerase chain reaction (qPCR) analysis of phenotype markers, quantification of lipid peroxidation (MDA), ROS, and Bodipy-based fluorescence imaging. Transcriptomic profiling was employed to delineate ferroptosis-associated pathways underlying macrophage polarization. The STEAP3/p53/SLC7A11 axis was validated by Western blot (WB) and qPCR. The effects of macrophage-conditioned medium on HPV16-positive SiHa cells were evaluated using a CCK-8 assay and a Transwell migration assay.

Results

ALA-PDT triggered macrophage M1 polarization with upregulated pro-inflammatory markers and induced macrophage ferroptosis, evidenced by elevated ferroptosis markers. Transcriptomic analysis revealed activation of ferroptosis pathways (STEAP3, p53, SLC7A11) in PDT-treated macrophages. Ferrostatin-1, a ferroptosis inhibitor, reversed PDT-induced reduction of M1 polarization. Conditioned medium from PDT-treated macrophages significantly reduced the relative metabolic activity and migration of SiHa cells.

Conclusion

ALA-PDT induces ferroptosis-dependent macrophage M1 polarization via the STEAP3/p53/SLC7A11 axis, potentiating macrophage-mediated elimination of HPV-infected cells. This ferroptosis-immunity interplay not only disrupts viral persistence but also provides a therapeutic paradigm to overcome HPV-driven immune suppression.

Abstract Image

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5-氨基乙酰丙酸光动力疗法通过STEAP3/p53/ slc7a11介导的铁凋亡促进M1巨噬细胞极化，治疗hpv相关疾病。

背景：人乳头瘤病毒（HPV）感染是各种恶性肿瘤的主要驱动因素，约占全世界宫颈癌病例的90%和口咽癌病例的70%，但对持续性病变的治疗仍然有限。5-氨基乙酰丙酸光动力疗法（ALA-PDT）通过活性氧（ROS）介导的细胞凋亡和免疫调节消除hpv感染细胞，但其免疫调节机制尚不清楚。方法：通过表型标记定量聚合酶链反应（qPCR）分析、脂质过氧化（MDA）定量、ROS定量和基于bodipi的荧光成像来表征巨噬细胞极化和铁凋亡。转录组学分析被用来描述巨噬细胞极化下的铁凋亡相关途径。通过Western blot （WB）和qPCR对STEAP3/p53/SLC7A11轴进行验证。使用CCK-8实验和Transwell迁移实验评估巨噬细胞条件培养基对hpv16阳性SiHa细胞的影响。结果：ALA-PDT触发巨噬细胞M1极化，促炎标志物上调，诱导巨噬细胞铁下垂，铁下垂标志物升高。转录组学分析显示，在pdt处理的巨噬细胞中，铁下垂途径（STEAP3, p53, SLC7A11）被激活。铁抑素-1，一种铁下垂抑制剂，逆转pdt诱导的M1极化减少。pdt处理巨噬细胞的条件培养基显著降低SiHa细胞的相对代谢活性和迁移。结论：ALA-PDT通过STEAP3/p53/SLC7A11轴诱导凋亡依赖性巨噬细胞M1极化，增强巨噬细胞介导的hpv感染细胞的消除。这种嗜铁-免疫相互作用不仅破坏了病毒的持久性，而且为克服hpv驱动的免疫抑制提供了一种治疗范例。

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来源期刊

Photodiagnosis and Photodynamic Therapy ONCOLOGY-

CiteScore

5.80

自引率

24.20%

发文量

509

审稿时长

50 days

期刊介绍： Photodiagnosis and Photodynamic Therapy is an international journal for the dissemination of scientific knowledge and clinical developments of Photodiagnosis and Photodynamic Therapy in all medical specialties. The journal publishes original articles, review articles, case presentations, "how-to-do-it" articles, Letters to the Editor, short communications and relevant images with short descriptions. All submitted material is subject to a strict peer-review process.