Modulating macrophage-mediated programmed cell removal: An attractive strategy for cancer therapy

Area of Science:

• Immunology and Cancer Biology
• Cellular Biology
• Molecular Biology

Background:

• Macrophage-mediated programmed cell removal (PrCR) is vital for tissue homeostasis, relying on a balance of pro-phagocytic ("eat me") and anti-phagocytic ("don't eat me") signals.
• Tumourigenesis and progression are linked to dysregulated PrCR, where the tumor microenvironment utilizes signals like CD47/SIRPα to evade immune detection.
• Effective PrCR induction requires overcoming immune escape mechanisms within the tumour microenvironment.

Purpose of the Study:

• To comprehensively review PrCR-activating and inhibiting signal molecules and their interactions.
• To highlight molecular mechanisms regulating immune function through PrCR modulation.
• To discuss advances and challenges in tumour therapy targeting PrCR.

Main Methods:

• Review of literature on PrCR signaling pathways.
• Analysis of molecular interactions between "eat me" and "don't eat me" signals.
• Examination of the Warburg effect in relation to PrCR.

Main Results:

• Identified key PrCR-activating molecules (CRT, PS, Annexin1, SLAMF7) and inhibiting molecules (CD47/SIRPα, MHC-I/LILRB1, CD24/Siglec-10, etc.).
• Elucidated molecular mechanisms by which PrCR is modulated in the tumour microenvironment.
• Summarized current research on tumour therapy strategies that activate PrCR.

Conclusions:

• Targeting the balance of PrCR signals presents a novel anti-tumour strategy.
• Understanding molecular regulators of PrCR is crucial for developing effective cancer therapies.
• Further research is needed to overcome challenges and optimize PrCR-targeted cancer treatments.