Newly Identified Biomarkers May Predict Treatment Response of NSCLC Patients to Chemoimmunotherapy


Cutting-edge cancer treatments such as immunotherapy, often combined with more conventional approaches such as chemotherapy, are offering patients new hope. However, determining the optimal combination of treatments is not always straightforward. Many patients spend valuable time on expensive treatments with significant side effects that are ineffective against cancer.

New discoveries are now ready to serve. Researchers at USC Norris Comprehensive Cancer Center have identified biomarkers that indicate which patients with non-small cell lung cancer (NSCLC) respond well to chemoimmunotherapy. This biomarker, known as CX3CR1, is expressed on her T cells and can be detected with a simple blood test six to nine weeks after the patient begins treatment.The results were published in a journal cancer research communication.

We 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 in these patients. ”


Fumito Ito, MD, lead author of the study, Associate Professor of Surgery, Keck School of Medicine, University of Southern California, and co-leader of the Translational and Clinical Sciences Research Program at the University of Southern California Norris Cancer Center

Ito and his team collected serial blood samples from 29 NSCLC patients who received a combination of immune checkpoint inhibitor (ICI) therapy and chemotherapy. They found that patients with elevated CX3CR1 levels after 6 and 9 weeks of treatment were more likely to see long-term benefits from chemoimmunotherapy, such as tumor shrinkage and cancer remission.

This finding builds on previous work by Ito and his team published in 2021 that found that CX3CR1 can be used to predict treatment response in NSCLC patients receiving immunotherapy alone. This biomarker could also be useful in other cancers and treatments, ultimately helping doctors and patients determine the most effective cancer treatments while avoiding unnecessary side effects and invasive biopsies. can help you decide.

“Early” therapeutic biomarkers

ICI therapy has revolutionized the treatment of lung and other cancers, but it does not work for all patients. In some people, it can also cause autoimmune reactions that can cause life-threatening problems in the lungs, liver, kidneys, and other organs.

Current pretreatment methods for determining which patients benefit from ICI treatment and which experience adverse side effects do not always work. CX3CR1 is a next-best, non-invasive ‘early’ therapeutic biomarker. This can be measured when the patient attends her first exam and imaging appointment, usually about 2 months after her ICI initiation.

“If the ICI is not working, we want to stop it as soon as possible,” Ito said. “Because patients with NSCLC have other viable treatment options, biomarkers can help identify patients who may benefit from alternative therapies.”

Ito et al. used a multi-omics approach that combined two state-of-the-art sequencing methods to find genomic and transcriptome signatures of T cells. Each T cell has a unique receptor pattern that can be used as a “barcode” to track her T cells in different parts of the body, such as those attacking tumors or circulating in the blood. .

“By combining two different types of next-generation sequencing, we have found a way to characterize and monitor T cells in patients,” he said. “Next, we plan to use this analysis in a larger cohort to see if other cancer patients respond similarly.”

Further evidence for CX3CR1

Because ICI therapy targets the patient’s immune system rather than the tumor itself, the newly discovered biomarkers may have broad application across multiple types of cancer. In addition to testing other cancers, Ito and colleagues will also investigate whether CX3CR1 can predict treatment response to other types of immunotherapy, such as adoptive T-cell therapy and vaccine-based therapies.

The research team also plans to collect additional evidence for CX3CR1 in a larger group of non-small cell lung cancer patients undergoing ICI with or without chemotherapy. If additional research is successful, blood tests for biomarkers could be made available to a broader patient population within two to three years, Ito said.

sauce:

University of Southern California Keck School of Medicine

Reference magazines:

Abdelfata, E. other. (2023). Predictive and prognostic impact of circulating CX3CR1+ CD8+ T cells in non-small cell lung cancer patients treated with chemoimmunotherapy. cancer research communication. doi.org/10.1158/2767-9764.crc-22-0383



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