Leandersson Karin, Blomgård Dag, Tuvesson Oscar, Rydén Lisa, Bergenfelz Caroline, Larsson Anna-Maria
Cancer Immunology, Department of Translational Medicine, Lund University, Malmö, Sweden.
Division of Oncology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
Sci Rep. 2025 Jul 12;15(1):25270. doi: 10.1038/s41598-025-08854-x.
Tumor associated neutrophils (TANs) exert dual and opposing functions in tumors, acting pro-tumorigenic and anti-tumorigenic, depending on tumor progression, polarization state and subtype. Consequently, the prognostic impact of TANs in breast cancer is also contradictory. Since neutrophils are critically needed to fight infections in cancer patients, the mediators leading to tumor progression need more investigation as potential future targets. The neutrophil derived mediator myeloperoxidase (MPO) is a peroxidase with dual functions in tumors, acting both immune enhancing and suppressing. Patients with metastatic breast cancer (MBC) have aggressive tumors with a dismal prognosis and urgently need novel treatment strategies. Therefore, we here aimed to investigate the prognostic impact of TANs, MPO TANs and MPO non-neutrophils using a cohort with newly diagnosed MBC patients specifically. We show that high infiltration of MPO TANs and MPO non-neutrophils in the primary tumor (PT), was associated with clinicopathological features and worse prognosis in patients with MBC. However, only infiltration of MPO TANs showed independent prognostic impact in multivariable analysis adjusting for other prognostic factors in MBC. The results need to be validated in a larger cohort but suggests that MPO targeting strategies could be relevant in breast cancer patients with aggressive disease.
肿瘤相关中性粒细胞（TANs）在肿瘤中发挥双重且相反的作用，根据肿瘤进展、极化状态和亚型的不同，既具有促肿瘤作用，也具有抗肿瘤作用。因此，TANs对乳腺癌的预后影响也存在矛盾。由于癌症患者对抗感染至关重要地需要中性粒细胞，导致肿瘤进展的介质作为潜在的未来靶点需要更多研究。中性粒细胞衍生介质髓过氧化物酶（MPO）是一种在肿瘤中具有双重功能的过氧化物酶，兼具免疫增强和抑制作用。转移性乳腺癌（MBC）患者的肿瘤具有侵袭性，预后不佳，迫切需要新的治疗策略。因此，我们在此专门针对一组新诊断的MBC患者，旨在研究TANs、MPO+TANs和MPO-非中性粒细胞的预后影响。我们发现，原发性肿瘤（PT）中MPO+TANs和MPO-非中性粒细胞的高浸润与MBC患者的临床病理特征及较差预后相关。然而，在对MBC其他预后因素进行校正的多变量分析中，只有MPO+TANs的浸润显示出独立的预后影响。该结果需要在更大的队列中进行验证，但表明针对MPO的策略可能与患有侵袭性疾病的乳腺癌患者相关。
