Related Experiment Video
Updated: Jun 1, 2026
Encapsulation of Cancer Therapeutic Agent Dacarbazine Using Nanostructured Lipid Carrier
Published on: April 26, 2016
Dacarbazine promotes stromal remodeling and lymphocyte infiltration in cutaneous melanoma lesions
Alessandra Nardin1, Wing-Cheong Wong, Charlene Tow
1Singapore Immunology Network (SIgN), ASTAR, Singapore, Singapore. alessandra_nardin@immunol.a-star.edu.sg
Abstract:
Dacarbazine (DTIC) is the standard first-line drug for advanced stage melanoma, but it induces objective clinical responses in only 15% of patients. This study was designed to identify molecular changes specifically induced by treatment in chemo-sensitive lesions. Using global transcriptome analysis and immunohistochemistry, we analyzed cutaneous metastases resected from patients with melanoma before and after DTIC treatment. The treatment induced similar functional changes in different lesions from the same patient. Stromal and immune response-related genes were the most frequently upregulated, particularly in lesions that responded to treatment by stabilizing or regressing. T-cell infiltration and enhanced major histocompatibility complex class II expression were observed in a subset of patients. Stable, chemo-sensitive lesions exhibited activation of genetic programs related to extracellular matrix remodeling, including increased expression of secreted protein acidic and rich in cysteine (SPARC) by tumor cells. These events were associated with local response to treatment and with superior survival in our group of patients. In contrast, SPARC expression was downregulated in lesions resistant to DTIC. Thus, chemotherapy drugs originally selected for their direct cytotoxicity to tumor cells may also influence disease progression by inducing changes in the tumor microenvironment.
Insights
Dacarbazine treatment for melanoma can alter the tumor microenvironment, boosting immune responses and extracellular matrix remodeling in sensitive lesions. These changes, including SPARC expression, correlate with better patient survival.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Dacarbazine (DTIC) is a standard melanoma treatment with limited response rates.
- Understanding treatment-induced molecular changes is crucial for improving efficacy.
Purpose of the Study:
- To identify molecular alterations in chemo-sensitive melanoma lesions after DTIC treatment.
- To investigate the role of tumor microenvironment changes in treatment response and survival.
Main Methods:
- Global transcriptome analysis and immunohistochemistry on melanoma metastases before and after DTIC treatment.
- Analysis of molecular changes in chemo-sensitive versus chemo-resistant lesions.
Main Results:
- DTIC treatment induced similar functional changes across lesions within patients.
- Upregulation of stromal and immune response genes, T-cell infiltration, and MHC class II expression were observed in responsive lesions.
- Chemo-sensitive lesions showed activation of extracellular matrix remodeling pathways, including increased secreted protein acidic and rich in cysteine (SPARC) expression.
- SPARC downregulation was noted in DTIC-resistant lesions.
Conclusions:
- DTIC influences melanoma progression by modulating the tumor microenvironment, not just direct cytotoxicity.
- Increased SPARC expression and immune/stromal gene activation in chemo-sensitive lesions are linked to better outcomes.
- Targeting tumor microenvironment modifications may enhance melanoma treatment strategies.
