Embracing diversity: macrophage complexity in cancer

Area of Science:

• Immunology
• Cancer Biology
• Cellular Biology

Background:

• Macrophages, specifically tumor-associated macrophages (TAMs), are myeloid cells integral to tumor progression.
• TAMs actively influence tumor evolution through complex cellular interactions and functional programs.
• Understanding the heterogeneity and plasticity of TAMs is critical for advancing cancer research.

Purpose of the Study:

• To review the diversity of TAMs, considering both single-cell phenotypes and physiological signals.
• To integrate current knowledge on TAM complexity and plasticity within the tumor microenvironment.
• To highlight the need for models that capture the full spectrum of TAM biology.

Main Methods:

• Review of existing literature on macrophage biology in cancer.
• Analysis of data from single-cell and spatial transcriptomics studies.
• Integration of physiological signals influencing TAM states and functions.

Main Results:

• TAMs exhibit significant longitudinal and local heterogeneity in their states and functions.
• TAMs possess capacities to sculpt tumors beyond simple cellular proliferation.
• Current models often lack the complexity to fully represent TAM biology.

Conclusions:

• A comprehensive understanding of TAM diversity requires integrating single-cell phenotypes with complex physiological cues.
• Further research into TAM plasticity is essential for developing effective cancer therapies.
• Advanced models are needed to fully elucidate the fundamental functional programs of TAMs.