Potential therapeutic effect of low-dose paclitaxel in melanoma patients resistant to immune checkpoint blockade: A pilot study
Checkpoint inhibitors are approved treatments for melanoma, helping the immune system kill melanoma cancer cells in a minority of patients. However, it is presumed that cancer cells in general, next to activating the immune system, also suppress it at the same time.
The team of Prof. Umansky showed that paclitaxel in low doses can decrease chronic inflammation and suppression of the immune system, and thus increase the activity of the immune system, making the body more susceptible to treatment and stronger to fight the cancer cells.
This pilot trial aimed at evaluating immuno-modulating effects, safety and efficacy of palliative treatment with ultra-low dose paclitaxel in 12 patients with metastatic melanoma in stage IV or III that cannot be treated with surgery.
The trial was completed in 2016. The median OS was 8.8 months. Since the recruited patients had a poor overall prognosis, the treatment response was good (2 PR, 1 SD; 6 PD). In responding patients, paclitaxel decreased the frequency and immunosuppressive pattern of myeloid-derived suppressor cells (MDSCs) in the peripheral blood and skin metastases evaluated by PD-L1 expression and nitric oxide (NO) production. In addition, paclitaxel modulated the production of inflammatory mediators in serum of melanoma patients. Responders displayed an increase in the frequency of tumour-infiltrating CD8+ T cells and their activity indicated by the upregulation of CD25 and TCR -chain expression. This study suggests that the treatment with low-dose paclitaxel could improve clinical outcome of advanced melanoma patients by enhancing anti-tumour immunity.
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