Tumor-Associated Macrophages (TAMs) in Cancer: Functional Programs, Metastatic Mechanisms, and Therapeutic Targeting

Area of Science:

• Immunology
• Oncology
• Cancer Biology

Background:

• Tumor-associated macrophages (TAMs) are abundant in breast cancer, influencing tumor progression, metastasis, immune evasion, and treatment resistance.
• TAMs exist on a spectrum of states, not just M1/M2, shaped by origin, location, tumor genetics, and therapy.

Purpose of the Study:

• To review the multifaceted roles of TAMs in breast cancer progression and metastasis.
• To synthesize mechanistic and translational evidence on TAM biology and therapeutic targeting.

Main Methods:

• Lineage tracing
• Intravital imaging
• Single-cell and spatial profiling
• Clinical analyses

Main Results:

• TAMs orchestrate key steps of metastasis, including angiogenesis, invasion, intravasation, and immune suppression.
• TAMs impact chemotherapy and immunotherapy efficacy.
• Targeting TAMs involves strategies like CSF1/CSF1R blockade, CCL2/CCR2 inhibition, CD40 agonism, PI3Kγ inhibition, and CD47-SIRPα blockade.

Conclusions:

• Spatially and functionally defined TAM states are critical regulators of breast cancer metastasis and therapy response.
• Developing effective TAM-targeting strategies requires integrating tumor stage, metastatic niche, and treatment context for personalized approaches.