Stem cell factor produced by tumor cells expands myeloid-derived suppressor cells in mice
Wei-Chen Lee1, Pao-Yueh Hsu2, Hsiu-Ying Hsu2
1Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, 5, Fu-Hsing Street, Kwei-Shan Township, Taoyuan, Taiwan. weichen@cgmh.org.tw.
Abstract:
Immunotherapy is a novel treatment approach for cancers; however, its therapeutic effects are impeded by myeloid-derived suppressor cells (MDSCs). This study aimed to determine how MDSCs are expanded in cancer hosts. MDSCs were positive for Gr-1 and CD11b. Hepa1-6 hepatoma cells, EL4 lymphoma cells, and mice bearing Hepa1-6 hepatoma or lymphoma were examined. Following the inoculation of Hepa1-6 cells into the flanks of mice, a linear correlation was evident between the frequency of MDSCs in the spleen and tumor sizes. MDSC numbers diminished gradually and returned to the normal level within 3 weeks if the tumors were excised. To identify the cytokines produced by tumor cells that allowed expansion of MDSCs, cytokines in Hepa1-6 cell culture medium and murine serum were examined using a cytokine array. Stem cell factor (SCF) was implicated as the relevant cytokine. When recombinant SCF was added to the spleen cell culture medium, MDSC expansion could occur. In the presence of c-kit blockade, this effect of SCF was partially reversed. In conclusion, MDSCs can be expanded in tumor cells in a process that involves SCF released by tumor cells.
Insights
Myeloid-derived suppressor cells (MDSCs) hinder cancer immunotherapy. Tumor cells release stem cell factor (SCF), a key cytokine driving MDSC expansion in cancer hosts.
Area of Science:
- Oncology
- Immunology
- Cell Biology
Background:
- Immunotherapy offers novel cancer treatment strategies.
- Therapeutic efficacy is often limited by myeloid-derived suppressor cells (MDSCs).
- Understanding MDSC expansion mechanisms is crucial for improving cancer therapies.
Purpose of the Study:
- To investigate the mechanisms of MDSC expansion in cancer-bearing hosts.
- To identify specific factors produced by tumor cells that promote MDSC proliferation.
Main Methods:
- Analysis of MDSC frequency (Gr-1+, CD11b+) in spleen of tumor-bearing mice.
- Correlation studies between tumor size and MDSC levels.
- Cytokine array analysis of tumor cell culture medium and murine serum.
- In vitro experiments with recombinant stem cell factor (SCF) and c-kit blockade.
Main Results:
- MDSC frequency in the spleen linearly correlated with tumor size in Hepa1-6 hepatoma models.
- Tumor excision led to a gradual decrease in MDSC numbers to normal levels within 3 weeks.
- Stem cell factor (SCF) was identified as a key cytokine produced by tumor cells.
- Recombinant SCF induced MDSC expansion in spleen cell cultures, partially inhibited by c-kit blockade.
Conclusions:
- Tumor cells promote MDSC expansion through the release of stem cell factor (SCF).
- SCF-induced MDSC expansion involves the c-kit signaling pathway.
- Targeting the SCF/c-kit axis may offer a strategy to overcome MDSC-mediated immunosuppression in cancer.
Related Concept Videos
01:01Regulation of Hematopoietic Stem Cells
01:15Differentiation of Common Myeloid Progenitor Cells
02:23Abnormal Proliferation