Macrophages: Targets for next-generation cancer immunotherapy

Area of Science:

• Immunology
• Oncology
• Biotechnology

Background:

• Tumor-associated macrophages (TAMs) are key immune cells within tumors, displaying functional plasticity.
• TAM heterogeneity, influenced by origin, transcription, and microenvironment, creates a paradox where they can promote or eliminate cancer.
• Current therapeutic strategies are limited in effectively controlling TAM functions.

Purpose of the Study:

• To review next-generation strategies for therapeutically targeting TAMs.
• To explore methods for relieving TAM-driven immunosuppression and activating their tumoricidal potential.
• To discuss novel bioengineering approaches for precise macrophage manipulation.

Main Methods:

• Modulating "eat-me" pathways and targeted activation for TAM effectorization.
• Reprogramming TAMs via immune checkpoint inhibition, signaling, epigenetic, and metabolic rewiring.
• Targeting myeloid progenitors and utilizing bioengineered therapeutics like CAR T cells.

Main Results:

• Next-generation strategies offer dual goals: reducing immunosuppression and enhancing tumoricidal activity.
• Bioengineering advances provide precise control over macrophage biology.
• Targeting TAMs can augment anti-tumor T cell responses and establish independent immunity.

Conclusions:

• Therapeutic targeting of TAMs holds transformative potential for cancer treatment.
• Reprogramming TAMs can unleash their anti-cancer functions.
• Novel bioengineered approaches promise enhanced control and efficacy in cancer immunotherapy.