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Effect of lentinan on macrophage cytotoxicity against metastatic tumor cells
11st Institute of Pathology and Experimental Cancer Research, Semmelweis Medical University, Budapest, Hungary.
Abstract:
We studied the effect of lentinan, a fungal polysaccharide immunomodulator, on mouse peritoneal macrophages. The i.p. treatment of mice with 10 mg/kg lentinan affected the number, plastic-adherence, and endogen peroxidase activity of peritoneal cells. The cytotoxicity of lentinan-stimulated peritoneal macrophages was determined against several murine and human metastatic tumor targets: Lewis lung carcinoma (LLT) and two human melanomas, and was found to be significantly higher than that of the macrophages from control animals. However, the highly metastatic variant of LLT (LLT-HH) was resistant to the cytolytic effect of resident and lentinan-activated macrophages as well, indicating that the stimulation for cytotoxicity depends not only on the functional activity of the effector but also on the sensitivity of the target.
Insights
Lentinan, a fungal polysaccharide, enhances the cancer-fighting ability of mouse macrophages. However, highly metastatic cancer cells remain resistant, indicating target sensitivity is crucial for effective immunotherapy.
Area of Science:
- Immunology
- Pharmacology
- Oncology
Background:
- Lentinan is a fungal polysaccharide with known immunomodulatory properties.
- Macrophages play a critical role in the immune response against cancer.
- Understanding how lentinan affects macrophage function is important for cancer research.
Purpose of the Study:
- To investigate the effects of lentinan on mouse peritoneal macrophages.
- To assess the cytotoxicity of lentinan-activated macrophages against various cancer cell lines.
- To determine the influence of target cell characteristics on macrophage-mediated cytotoxicity.
Main Methods:
- Mice were treated with lentinan (10 mg/kg, i.p.).
- Peritoneal macrophages were isolated and analyzed for cell number, adherence, and peroxidase activity.
- Cytotoxicity assays were performed using lentinan-stimulated macrophages against Lewis lung carcinoma (LLT) and human melanoma cell lines, including a highly metastatic variant (LLT-HH).
Main Results:
- Lentinan treatment altered peritoneal macrophage characteristics (number, adherence, peroxidase activity).
- Lentinan-activated macrophages exhibited significantly higher cytotoxicity against LLT and human melanoma cells compared to controls.
- The highly metastatic LLT-HH variant demonstrated resistance to both resident and lentinan-activated macrophages.
Conclusions:
- Lentinan enhances the cytotoxic activity of mouse peritoneal macrophages against certain cancer targets.
- The sensitivity of the target tumor cells plays a significant role in the efficacy of macrophage-mediated immunotherapy.
- Further research is needed to overcome resistance in highly metastatic cancers.