Research Progress on Tumor-Associated Macrophages and PD-1/PD-L1 Inhibitors in Advanced Colorectal Cancer

Area of Science:

• Oncology
• Immunology
• Cancer Research

Background:

• Colorectal cancer (CRC) is a leading cause of cancer mortality globally.
• Surgical resection is standard for CRC, but advanced cases risk recurrence and metastasis.
• Immune checkpoint inhibitors (ICIs) show limited benefit in proficient mismatch repair/microsatellite stable (pMMR/MSS) CRC.

Purpose of the Study:

• To review the role of tumor-associated macrophages (TAMs) in mediating resistance to PD-1/PD-L1 inhibitors in CRC.
• To explore strategies for enhancing immunotherapy response through TAM modulation.
• To discuss current limitations and future research directions in TAM-targeted CRC therapy.

Main Methods:

• Narrative review of recent advances in TAM involvement in PD-1/PD-L1 blockade resistance.
• Analysis of mechanistic studies and clinical trial data.
• Focus on TAM modulation strategies for immunotherapy enhancement.

Main Results:

• TAMs contribute to immunosuppression and promote PD-1 expression, mediating resistance to PD-1/PD-L1 inhibitors in CRC.
• Evidence suggests TAMs play a critical role in limiting ICI efficacy in pMMR/MSS CRC.
• Mechanistic insights into TAM-mediated resistance are emerging but require further investigation.

Conclusions:

• TAMs are key players in CRC resistance to current immunotherapies.
• Targeting TAMs in combination with ICIs may overcome resistance and improve outcomes for pMMR/MSS CRC patients.
• Further research is needed to bridge the gap between mechanistic findings and clinical trial results for TAM-targeted therapies.