Journal
CELLULAR IMMUNOLOGY
Volume 360, Issue -, Pages -Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.cellimm.2020.104274
Keywords
Immunotherapy; Melanoma; Myeloid suppressor cells; Paclitaxel; Immune checkpoint blockade
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Funding
- Anticancer Fund, Belgium
- Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [259,332,240/RTG 2099]
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Low-dose paclitaxel treatment may improve clinical outcomes for some advanced melanoma patients by enhancing antitumor immunity, potentially suggesting its use in combined melanoma immunotherapy.
The low dose application of chemotherapeutic agents such as paclitaxel was previously shown to initiate antitumor 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 zeta-chain expression. Our study suggests that low-dose paclitaxel treatment could improve clinical outcome of some advanced melanoma patients by enhancing antitumor immunity and might be proposed for combined melanoma immunotherapy.
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