The Challenge: Immunotherapy and Colorectal Cancer
Immunotherapy has revolutionized the treatment of various cancers, including colorectal cancer. However, not every patient responds favorably to this therapy, making it imperative to find predictive markers for effective treatment.
This issue is particularly relevant for patients with metastatic colorectal cancer who have defective DNA repair systems, also known as mismatch repair.
The Study: Using Spatial Analysis of Proteins
In a breakthrough study published in the journal Clinical Cancer Research, researchers from the Mayo Clinic Comprehensive Cancer Center explored the utility of spatial analysis in predicting the effectiveness of PD-1 blockade immunotherapy.
The study focused on the proximity of cells that express immune checkpoint proteins programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1).
The study’s lead author, Dr. Frank Sinicrope, noted that if cells expressing PD-1 and PD-L1 were within 10 microns of each other in a tumor, then immunotherapy could significantly improve patient survival.
This suggests a critical threshold for the effective blockade of PD-1 and PD-L1 binding, which can be targeted by checkpoint inhibitors.
Implications for Treatment
According to the study, 60% of the examined patient tumors had a large number of cells where PD-1 and PD-L1 were in close proximity.
This implies that a substantial proportion of patients could benefit from PD-1 blockade immunotherapy. Conversely, the remaining 40% may need alternative or combination therapies.
This spatial analysis method has the potential to serve as a powerful tool for clinicians in selecting patients most likely to benefit from immunotherapy, thereby minimizing unnecessary treatments and their associated costs and toxicities.
Looking Forward
The team is currently in the process of validating their findings. If validated, this could be a game-changer in the way clinicians approach the treatment of colorectal cancer using immunotherapy.
“While our results are promising, the study data await validation in an independent cohort and are not yet ready to be used in clinical practice,” cautioned Dr. Sinicrope.
However, as the first report of its kind for colorectal cancer, this study opens new avenues for optimizing patient selection in immunotherapy treatments and offers a glimpse into the future of personalized cancer care.
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The study was published in Clinical Cancer Research.
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