Potential therapeutic effect of low-dose paclitaxel in melanoma patients resistant to immune checkpoint blockade: A pilot study
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Potential therapeutic effect of low-dose paclitaxel in melanoma patients resistant to immune checkpoint blockade: A pilot study. / Gebhardt, Christoffer; Simon, Sonja C S; Weber, Rebekka; Gries, Mirko; Mun, Dong Hun; Reinhard, Raphael; Holland-Letz, Tim; Umansky, Viktor; Utikal, Jochen.
in: CELL IMMUNOL, Jahrgang 360, 104274, 02.2021, S. 104274.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Potential therapeutic effect of low-dose paclitaxel in melanoma patients resistant to immune checkpoint blockade: A pilot study
AU - Gebhardt, Christoffer
AU - Simon, Sonja C S
AU - Weber, Rebekka
AU - Gries, Mirko
AU - Mun, Dong Hun
AU - Reinhard, Raphael
AU - Holland-Letz, Tim
AU - Umansky, Viktor
AU - Utikal, Jochen
N1 - Copyright © 2020 Elsevier Inc. All rights reserved.
PY - 2021/2
Y1 - 2021/2
N2 - 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.
AB - 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.
U2 - 10.1016/j.cellimm.2020.104274
DO - 10.1016/j.cellimm.2020.104274
M3 - SCORING: Journal article
C2 - 33383383
VL - 360
SP - 104274
JO - CELL IMMUNOL
JF - CELL IMMUNOL
SN - 0008-8749
M1 - 104274
ER -