Strategies to Predict Immunotherapy Benefit Among Patients With Advanced Colorectal Cancer

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Researchers have identified new strategies to help physicians predict which patients with advanced colorectal cancer may benefit from immunotherapy, according to a recent study published by Saberzadeh-Ardestani et al in Clinical Cancer Research. The findings demonstrate the potential of using spatial analyses of specific proteins as predictive tools for selecting appropriate candidates for PD-1 inhibitors—and may ultimately improve outcomes and eliminate unnecessary treatments.

Study Details

While immunotherapy continues to advance cancer treatment, not all patients with metastatic colorectal cancer who have mismatch repair deficiencies may benefit from this treatment. Accordingly, there is a need for predictive biomarkers of response and survival.

In the new study, the researchers discovered that the distance between cells that express PD-1 and PD-L1 within the tumor can help predict the outcome of immunotherapy in patients who have colorectal cancers with mismatch repair deficiencies. 

Among the tumors that were examined in the study, 60% of them had an increased number of cells with PD-1 and PD-L1 in close proximity—suggesting that 60% of these patients were likely to benefit from immunotherapy. The researchers proposed that such data may hold the potential to assist physicians in selecting patients for treatment, whereas the other 40% who may be less likely to benefit from immunotherapy could be treated with combination therapy or another type of treatment.


"The findings suggest that this spatial analysis within tumors may be useful to select patients who are more likely to benefit from immunotherapy," explained senior study author Frank Sinicrope, MD, a medical oncologist and gastroenterologist at the Mayo Clinic Comprehensive Cancer Center. "If cells expressing these proteins were at or within 10 microns of each other within the tumor, then immunotherapy treatment was able to significantly improve patient survival—[demonstrating] a critical threshold for effective blockade of the PD-1/PD-L1 axis,” he highlighted.

The researchers noted that they are currently validating their findings. If the results of their further analysis are positive, their new method would allow physicians to select patients most likely to benefit from PD-1 blockade and spare those least likely to benefit from experiencing the potential toxicities and drug costs of immunotherapy.

"To our knowledge, this is the first report of this finding in colorectal cancer; however, reports showing the importance of PD-1 and PD-L1 proximity have been reported in melanoma and non–small cell lung cancer," stated Dr. Sinicrope. "While our results are promising, the study data await validation in an independent cohort so are not yet ready to be used in clinical practice,” he concluded.

Disclosure: The research in this study was supported in part a grant from the National Cancer Institute and Roche Diagnostics. For full disclosures of the study authors, visit

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