The low dose application of chemotherapeutic agents such as paclitaxel was previously shown to initiate anti-tumor activity by neutralizing myeloid-derived suppressor cells (MDSCs) in melanoma mouse models. Here, we investigated immunomodulating effects of low-dose paclitaxel in 9 metastatic melanoma patients resistant to prior treatments. Three patients showed response to therapy (two partial responses and one stable disease). In responding patients, paclitaxel decreased the frequency and immunosuppressive pattern of MDSCs in the peripheral blood and skin metastases. Furthermore, paclitaxel modulated levels of inflammatory mediators in the serum. In addition, responders displayed enhanced frequencies of tumor-infiltrating CD8⁺ T cells and their activity indicated by the upregulation of CD25 and TCR ζ-chain expression. Our study suggests that low-dose paclitaxel treatment could improve clinical outcome of some advanced melanoma patients by enhancing anti-tumor immunity and might be proposed for combined melanoma immunotherapy.

先前显示低剂量应用化学治疗剂（例如紫杉醇）可通过中和黑素瘤小鼠模型中髓样来源的抑制细胞（MDSC）来启动抗肿瘤活性。在这里，我们调查了低剂量紫杉醇对9例对既往治疗有抵抗力的转移性黑色素瘤患者的免疫调节作用。3例患者对治疗有反应（2例局部缓解和1例稳定疾病）。在有反应的患者中，紫杉醇降低了外周血和皮肤转移中MDSC的频率和免疫抑制模式。此外，紫杉醇调节血清中炎症介质的水平。此外，反应者的肿瘤浸润CD8 ⁺频率更高CD25和TCRζ链表达的上调表明T细胞及其活性。我们的研究表明，小剂量紫杉醇治疗可通过增强抗肿瘤免疫力来改善某些晚期黑色素瘤患者的临床疗效，并可能被建议用于联合黑色素瘤免疫治疗。