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Myeloid progenitor cells mediate immune suppression in patients with head and neck cancers
1Research Service, Hines Veterans Affairs Hospital, IL 60141, USA. myoung1@wpo.it.luc.edu
Abstract:
Patients with squamous cell carcinomas of the head and neck (HNSCC) have profound defects in their immune defenses. We have shown that among the mechanisms that contribute to this immune dysfunction are immune inhibitory CD34+ progenitor cells, whose levels become elevated in the peripheral blood and within the tumor tissue. One goal of our studies is to overcome the immune inhibitory activities of tumor-induced CD34+ progenitor cells by stimulating their differentiation into cells, such as dendritic or monocytic cells, that can stimulate immune reactivity to autologous cancer. Results of in vitro analyses with CD34+ suppressor cells of HNSCC patients and of in vivo studies in animal tumor models have shown the capacity of tumor-induced CD34+ cells to differentiate into cells that phenotypically resemble monocytic or dendritic cells. Whether these cells can differentiate into dendritic cells in HNSCC patients is currently being tested. Less clear is whether the pathway by which the tumor-induced CD34+ cells differentiate will result in cells having the full capacity to function as potent stimulators of immune reactivity to autologous tumor.
Insights
Head and neck cancer patients have immune defects due to elevated CD34+ progenitor cells. Stimulating these cells to differentiate may restore immune responses against cancer.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- Squamous cell carcinomas of the head and neck (HNSCC) are associated with significant immune dysfunction.
- Elevated levels of immune-inhibitory CD34+ progenitor cells are observed in the peripheral blood and tumor tissue of HNSCC patients.
Purpose of the Study:
- To investigate methods to overcome the immune suppressive activities of tumor-induced CD34+ progenitor cells in HNSCC.
- To stimulate the differentiation of CD34+ progenitor cells into immune-stimulatory cells like dendritic or monocytic cells.
Main Methods:
- In vitro analyses of CD34+ suppressor cells from HNSCC patients.
- In vivo studies utilizing animal tumor models.
Main Results:
- Tumor-induced CD34+ cells demonstrated the capacity to differentiate into cells resembling monocytic or dendritic cells.
- Differentiation potential was observed in both in vitro patient cell studies and in vivo animal models.
Conclusions:
- CD34+ progenitor cells in HNSCC patients can be induced to differentiate into potentially immune-stimulatory cell types.
- Further research is needed to confirm the functional capacity of these differentiated cells to stimulate anti-tumor immune responses in patients.