Targeting the myeloid microenvironment in neuroblastoma

Area of Science:

• Immunology
• Oncology
• Cell Biology

Background:

• Myeloid cells, including granulocytes and monocytes/macrophages, are crucial in neuroblastoma development and progression.
• These cells create an immunosuppressive network, hindering the adaptive immune system's ability to combat high-risk neuroblastoma.
• Myeloid-derived suppressor cells (MDSC) contribute significantly to this immunosuppression.

Purpose of the Study:

• To review the dual roles (pro- and anti-tumorigenic) of myeloid cells in neuroblastoma.
• To examine the involvement of myeloid cells in current neuroblastoma treatments.
• To explore novel therapeutic strategies targeting myeloid cells in neuroblastoma.

Main Methods:

• Literature review summarizing myeloid cell functions in neuroblastoma.
• Analysis of myeloid cell engagement in existing treatment regimens.
• Exploration of emerging strategies to target myeloid cells.

Main Results:

• Tumor-associated myeloid cells can be leveraged as effector cells, particularly in anti-GD2 immunotherapy.
• Targeting axes like CD47/SIRPα can enhance myeloid cell engagement.
• Depleting or blocking myeloid cell infiltration can be effective but may also remove beneficial effector cells.

Conclusions:

• Reprogramming suppressive myeloid cells is a potentially optimal strategy.
• This approach can reverse immunosuppressive traits while preserving effector functions.
• Reactivating tumor-infiltrating T cells is a key outcome of myeloid cell reprogramming.