Human Tumor-Infiltrating Myeloid Cells: Phenotypic and Functional Diversity

Area of Science:

• Oncology
• Immunology
• Cell Biology

Background:

• Current understanding of tumor-resident myeloid cells largely relies on murine models and immunohistochemistry (IHC).
• This has led to a simplified view of myeloid cells as either protumor M2 macrophages or myeloid-derived suppressor cells (MDSC).
• Limitations of IHC restrict the analysis of myeloid cell phenotype and function in the tumor microenvironment.

Purpose of the Study:

• To critically review human myeloid cell nomenclature in cancer.
• To examine criteria defining human tumor-infiltrating myeloid cell subsets.
• To highlight new evidence on myeloid cell contributions to cancer pathogenesis from clinical studies.

Main Methods:

• Comprehensive review of existing literature on human myeloid cells in cancer.
• Critical analysis of myeloid cell nomenclature and classification.
• Comparison of human clinical data with murine models.
• Review of tumor-regulation mechanisms and therapeutic targeting of myeloid cells.

Main Results:

• The simplified protumor M2/MDSC paradigm inadequately captures the complexity of human tumor-resident myeloid cells.
• Human myeloid cell phenotypes and functions in the tumor microenvironment are more diverse than previously recognized.
• Clinical studies reveal nuanced roles of myeloid cells in cancer pathogenesis, distinct from murine models.

Conclusions:

• Re-evaluation of human myeloid cell classification and function is crucial for advancing cancer research.
• Understanding the complexity of myeloid cells in the human tumor microenvironment is essential for developing effective cancer therapies.
• Targeting myeloid cell regulatory mechanisms offers promising therapeutic avenues.