An “early-on” treatment biomarker
ICI therapy has revolutionized the treatment of lung and other cancers, but it doesn’t work for all patients. For some, it can even trigger an autoimmune reaction marked by life-threatening problems with the lungs, liver, kidneys, or other organs. Current pre-treatment methods to deter- mine which patients will benefit from ICI therapy – and which will experience harmful side effects – don’t always work. CX3CR1 is the next best thing: an “early-on” treatment biomarker that is noninvasive. It can be measured when patients attend their first check-up and imaging appointment, typically about two months after starting ICI.
“If ICI is not working, we like to stop as soon as possible,” Ito said. “We have other viable treatment options for NSCLC patients, so the biomarker can help us identify patients who might have better results with an alternative therapy.”
Ito and his colleagues used a multi-omics approach, combining two cutting-edge sequencing methods to find the genomic and transcriptomic signature of T-cells. Each T-cell has a unique receptor pattern that can be used as a “barcode” to track them down in different parts of the body, including those attacking a tumour 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 will respond in a similar way.”
More evidence for CX3CR1
Because ICI therapy targets a patient’s immune system, rather than the tumour itself, the newly discovered biomarker could have broad utility 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 collect additional evidence for CX3CR1 in a larger group of non-small cell lung cancer patients undergoing ICI, both with and without chemotherapy. If additional research is successful, a blood test for the biomarker could reach broader patient populations in two to three years, Ito said.
1. Eihab Abdelfatah, Mark D. Long, Ryutaro Kajihara, e. al.; Predictive and Prognostic Implications of Circulating CX3CR1+ CD8+ T Cells in Non–Small Cell Lung Cancer Patients Treated with Chemo-Immunotherapy. Cancer Research Communications
1 March 2023; 3 (3): 510–520. https://doi.org/10.1158/2767-9764.CRC-22-0383
2. Yamauchi, T., Hoki, T., Oba, T. et al. T-cell CX3CR1 expression as a dynamic blood-based biomarker of response to immune checkpoint inhibitors. Nature Communications 12, 1402 (2021). https://doi.org/10.1038/s41467-021-21619-0