Cutting-edge cancer treatments such as immunotherapy offer new hope to patients, and are often combined with more common approaches such as chemotherapy. But determining the best treatment combination is not always easy. Many patients spend precious time on expensive treatments that have dangerous side effects and are ineffective against cancer.
Now, a new discovery is about to help. Researchers from the USC Norris Comprehensive Cancer Center have identified a biomarker that indicates patients with non-small cell lung cancer (NSCLC) will respond well to immunochemotherapy. The biomarker, known as CX3CR1, is expressed on T cells and can be detected with a simple blood test, six to nine weeks after a patient begins treatment. The results have been published in the journal Cancer Research Communications.
We’ve found that T cell CX3CR1 expression can be used to monitor treatment efficacy, and can be used as a biomarker to predict treatment response and prognosis for these patients.”
Fumito Ito, MD, PhD, lead author of the study, assistant professor of surgery in the Keck School of Medicine at USC and co-chair of the Translational and Clinical Science Research Program at USC Norris Cancer Center
Ito and his team collected a series of blood samples from 29 patients with NSCLC who received a combination of treatment with immune checkpoint inhibitors (ICI) and chemotherapy. They found that patients who had elevated levels of CX3CR1 after six and nine weeks of treatment were more likely to see long-term benefits from immunochemotherapy, including tumor shrinkage and cancer remission.
The findings build on previous work by Ito and his team, published in 2021, which found that CX3CR1 can be used to predict treatment response in NSCLC patients who only receive immunotherapy. The biomarker may also be useful for other types of cancer and therapies and could ultimately help doctors and patients determine the most effective cancer treatments while avoiding unnecessary side effects and invasive biopsies.
An ‘early’ therapeutic biomarker
ICI therapy has revolutionized the treatment of lung diseases and other types of cancer, but it doesn’t work for all patients. For some, it can even trigger an autoimmune reaction marked by life-threatening problems in the lungs, liver, kidneys, or other organs.
Existing pretreatment methods to identify patients who would benefit from ICSI treatment – ; and which ones will experience adverse side effects -; It doesn’t always work. CX3CR1 is the next best thing: a biomarker for “early” non-invasive therapy. It can be measured when patients attend their first screening and imaging appointment, usually about 2 months after the start of ICSI.
“If the ICI program isn’t working, we’d love to stop as soon as possible,” Ito said. “We have other viable treatment options for NSCLC patients, so this biomarker can help us identify patients who may have a better outcome with alternative therapy.”
Ito and colleagues used a multiscale approach, combining two well-developed sequencing methods to find the genomic and transcriptional signature of T cells. Each T cell has a unique pattern of receptors that can be used as a “barcode” to track them to different parts of the body, including those attacking a tumor and those circulating in the blood.
“By combining two different types of next-generation sequencing, we found a way to characterize and monitor patients’ T cells,” he said. “Next, we plan to use this analysis in a larger cohort to see if patients with other cancers would respond in a similar way.”
More evidence for CX3CR1
Because ICI treatment targets the patient’s immune system, rather than the tumor itself, the newly discovered biomarker could have broad benefit across multiple types of cancer. In addition to testing other cancers, Ito and his colleagues also plan to explore whether CX3CR1 can predict treatment response to other types of immunotherapy, including adoptive T-cell therapy and vaccine-based therapy.
The team will also gather additional evidence for CX3CR1 in a larger group of non-small cells Lung cancer patients Undergoing ICI, either with or without chemotherapy. If additional research is successful, Ito said, the blood test for the biomarker could reach more patients within two to three years.
Abdel-Fattah, E.; et al. (2023). Predictive and prognostic effects of CX3CR1+CD8+ T cell proliferation in non-small cell lung cancer patients treated with immunochemotherapy. Cancer Research Communications. doi.org/10.1158/2767-9764.crc-22-0383