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Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine
Published on: February 24, 2023
Potential therapeutic effect of low-dose paclitaxel in melanoma patients resistant to immune checkpoint blockade: A
Christoffer Gebhardt1, Sonja C S Simon2, Rebekka Weber2
1Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany; Department of Dermatology and Venereology, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany.
Abstract:
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.
Insights
Low-dose paclitaxel therapy shows promise for advanced melanoma patients by reducing immunosuppressive cells and boosting anti-tumor immunity. This approach may enhance patient response when combined with immunotherapy.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Low-dose paclitaxel demonstrated anti-tumor effects by neutralizing myeloid-derived suppressor cells (MDSCs) in preclinical melanoma models.
- Metastatic melanoma often exhibits resistance to conventional therapies, necessitating novel treatment strategies.
Purpose of the Study:
- To investigate the immunomodulatory effects of low-dose paclitaxel in patients with advanced metastatic melanoma.
- To assess the impact of low-dose paclitaxel on MDSCs, inflammatory mediators, and anti-tumor T cell responses.
Main Methods:
- Treatment of 9 metastatic melanoma patients with low-dose paclitaxel.
- Analysis of peripheral blood and skin metastasis samples to evaluate MDSC frequency and phenotype.
- Serum analysis for inflammatory mediators.
- Assessment of tumor-infiltrating CD8+ T cell frequency and activation markers (CD25, TCR ζ-chain).
Main Results:
- Three out of nine patients responded to low-dose paclitaxel (two partial responses, one stable disease).
- Responders exhibited decreased MDSC frequency and immunosuppressive patterns in blood and metastases.
- Paclitaxel modulated serum inflammatory mediators.
- Responders showed increased tumor-infiltrating CD8+ T cells with enhanced activity.
Conclusions:
- Low-dose paclitaxel can enhance anti-tumor immunity in some advanced melanoma patients.
- The observed immunomodulation suggests potential for low-dose paclitaxel in combination melanoma immunotherapy.
- This approach may improve clinical outcomes for treatment-resistant melanoma.
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