Measuring the Distance Between Cells Can Help Predict Immunotherapy Effectiveness in CRC

Measuring the distance between certain types of cells may help predict which patients with advanced colorectal cancer are less likely to benefit from immunotherapy treatment, according to findings from recent research.

A study published in the journal, Clinical Cancer Research, established that immunotherapy may not be the best treatment option for some patients with advanced colorectal cancer. By avoiding potentially ineffective drugs, patients will not have to bear the burden of the cost or experience potential toxicity from the drug, according to a press release from Mayo Clinic.

The study’s researchers, who are from Mayo Clinic Comprehensive Cancer Center, found that using spatial analysis (measuring the distance between cells within a tumor) can help predict whether immunotherapy is appropriate for patients with advanced colorectal cancer.

Specifically, researchers analyzed the distance between the cells that express programmed cell death protein 1 (PD-1; an immune checkpoint protein that helps regulate the immune system’s responses) and programmed cell death ligand 1 (PD-L1; an immune checkpoint protein that slows and maintains the control of the immune system’s responses) within tumors that had a defective DNA repair system (dMMR).

PD-1 and PD-L1 proteins are located on immune cells, with an abundance of these proteins on some types of cancer cells, according to National Cancer Institute. Drugs called checkpoint inhibitors — commonly referred to as immunotherapy agents in the cancer space — block one or both of these proteins when they are bound together.

“The finding suggests that this spatial analysis within tumors may be useful to select patients who are more likely to benefit from immunotherapy,” Dr. Frank Sinicrope, medical oncologist, gastroenterologist at Mayo Clinic Comprehensive Cancer Center and lead study author, said in the press release. “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. This finding suggests a critical threshold for effective blockade of the PD-1/PD-L1 axis.”

The findings from the respective study, reported in the press release, determined that among the patient tumors that were analyzed, 60% of patients had an increased number of cells with PD-1 and PD-L1 that were close together. This meant that 60% of patients were more likely to benefit from receiving immunotherapy.

The researchers also found that their data had potential to support doctors with selecting patients who need immunotherapy, according to the press release. They noted that the remaining 40% of patients who would not benefit from receiving immunotherapy could be treated with combination therapy or a different type of treatment, avoiding immunotherapy altogether.

Although this finding may offer a significant change for patients with advanced colorectal cancer, there are still unmet needs regarding predictive biomarkers (a measurement to detect how well the body responds to treatment for a disease) of response and survival, Sinicrope stated.

“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,” said 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.”

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