Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark.
LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
Blood. 2019 Sep 26;134(13):1072-1083. doi: 10.1182/blood.2018888107. Epub 2019 Jul 22.
It has been proposed that CD4 T-cell responses to (SA) can inadvertently enhance neoplastic progression in models of skin cancer and cutaneous T-cell lymphoma (CTCL). In this prospective study, we explored the effect of transient antibiotic treatment on tumor cells and disease activity in 8 patients with advanced-stage CTCL. All patients experienced significant decrease in clinical symptoms in response to aggressive, transient antibiotic treatment. In some patients, clinical improvements lasted for more than 8 months. In 6 of 8 patients, a malignant T-cell clone could be identified in lesional skin, and a significant decrease in the fraction of malignant T cells was observed following antibiotics but an otherwise unchanged treatment regimen. Immunohistochemistry, global messenger RNA expression, and cell-signaling pathway analysis indicated that transient aggressive antibiotic therapy was associated with decreased expression of interleukin-2 high-affinity receptors (CD25), STAT3 signaling, and cell proliferation in lesional skin. In conclusion, this study provides novel evidence suggesting that aggressive antibiotic treatment inhibits malignant T cells in lesional skin. Thus, we provide a novel rationale for treatment of SA in advanced CTCL.
有人提出,CD4 T 细胞对金黄色葡萄球菌(SA)的反应可能会无意中促进皮肤癌和皮肤 T 细胞淋巴瘤(CTCL)模型中的肿瘤进展。在这项前瞻性研究中,我们探讨了短期抗生素治疗对 8 例晚期 CTCL 患者肿瘤细胞和疾病活动的影响。所有患者在接受积极的短期抗生素治疗后,临床症状均显著减轻。在一些患者中,临床改善持续了 8 个月以上。在 8 例患者中有 6 例可在皮损皮肤中识别出恶性 T 细胞克隆,并且在使用抗生素后观察到恶性 T 细胞的比例显著降低,但其他治疗方案保持不变。免疫组化、全局信使 RNA 表达和细胞信号通路分析表明,短期积极的抗生素治疗与皮损皮肤中白细胞介素-2 高亲和力受体(CD25)、STAT3 信号和细胞增殖的表达降低有关。总之,这项研究提供了新的证据表明,积极的抗生素治疗可抑制皮损皮肤中的恶性 T 细胞。因此,我们为晚期 CTCL 中金黄色葡萄球菌的治疗提供了新的依据。