Overcoming resistance to anti-PD-L1 immunotherapy: mechanisms, combination strategies, and future directions.

This publication reviews the complex role of PD-L1 in cancer immunotherapy, focusing on its regulation, interaction with the immune system, and mechanisms of resistance to anti-PD-L1 therapies.

Despite the promise of anti-PD-1/PD-L1 treatments, their limited efficacy highlights the need to understand and overcome resistance.

The review discusses emerging strategies, including:

• Combination therapies
• Tumor microenvironment modulation
• Neoantigen targeting
• Dynamic biomarker monitoring using advanced technologies such as high-resolution imaging, machine learning, multi-omics, and liquid biopsy

It also covers ongoing clinical trials combining immune checkpoint inhibitors with:

• Chemotherapy
• Radiotherapy
• Targeted agents
• CAR-T therapies
• Metabolic immunotherapies

These insights aim to enhance personalized immunotherapy approaches to improve patient outcomes.