CX3CR1 biomarker may help doctors personalize cancer treatment

Exciting breakthroughs in cancer treatment, such as immunotherapy, have provided renewed hope for patients, often in combination with traditional methods like chemotherapy. However, determining the optimal treatment combination can be challenging. Many patients endure costly therapies with severe side effects that prove ineffective against their specific cancer.

Fortunately, a recent discovery is poised to alleviate this predicament. Scientists from USC Norris Comprehensive Cancer Center have identified a promising biomarker that can indicate which non-small cell lung cancer (NSCLC) patients will respond favorably to chemoimmunotherapy. Known as CX3CR1, this biomarker is expressed on T-cells and can be detected through a simple blood test conducted six to nine weeks after treatment initiation. The findings of this study were published in the esteemed journal Cancer Research Communications.

Lead author Dr. Fumito Ito, an associate professor of surgery at the Keck School of Medicine of USC and co-leader of the Translational and Clinical Science Research program at the USC Norris cancer center, explains the significance of their research: “We have determined that T-cell CX3CR1 expression can be utilized to assess treatment effectiveness. This biomarker holds great promise in predicting treatment response and prognosis for NSCLC patients.”

To arrive at their conclusions, Dr. Ito and his team collected a series of blood samples from 29 NSCLC patients who underwent a combination of immune checkpoint inhibitor (ICI) therapy and chemotherapy. They discovered that patients with elevated levels of CX3CR1 after six and nine weeks of treatment exhibited a greater likelihood of experiencing long-term benefits from chemoimmunotherapy, such as tumor shrinkage and cancer remission.

These findings build upon Dr. Ito’s earlier work, published in 2021, which demonstrated that CX3CR1 could predict treatment response in NSCLC patients undergoing immunotherapy alone. The biomarker may also prove useful in assessing other types of cancers and therapies. Ultimately, it has the potential to assist physicians and patients in determining the most effective course of cancer treatment, while minimizing unnecessary side effects and invasive biopsies.

An “early-on” treatment biomarker

Immunotherapy, known as ICI therapy, has revolutionized cancer treatment, but its effectiveness varies among patients, and in some cases, it can even trigger severe autoimmune reactions affecting vital organs like the lungs, liver, and kidneys.

Currently, pre-treatment methods to determine ICI therapy’s suitability and potential side effects are not always reliable. However, the discovery of the CX3CR1 biomarker presents a promising solution. This biomarker acts as an early indicator of treatment response and is noninvasive, making it an ideal candidate for assessing patients’ suitability for ICI therapy. Typically measured during the first check-up and imaging appointment, around two months after initiating ICI therapy, CX3CR1 can help identify patients who are unlikely to benefit from this specific treatment, enabling timely intervention with alternative therapies.

Dr. Fumito Ito and his team employed a multi-omics approach, utilizing two advanced sequencing methods to uncover the genomic and transcriptomic signatures of T-cells. Since each T-cell possesses a unique receptor pattern, it can be tracked like a barcode throughout the body, including T-cells engaged in attacking tumors and those circulating in the bloodstream.

“Our integration of two distinct next-generation sequencing techniques has allowed us to characterize and monitor patients’ T-cells,” explained Dr. Ito. “Our next step involves expanding this analysis to a larger cohort to determine if patients with other types of cancer exhibit a similar response.”

This groundbreaking research opens up avenues for tailoring treatment plans based on individual patient characteristics, thereby optimizing outcomes and reducing the risk of unnecessary adverse effects.

More evidence for CX3CR1

The newly discovered biomarker, CX3CR1, holds significant potential in the realm of cancer treatment beyond non-small cell lung cancer (NSCLC). Since ICI therapy targets the patient’s immune system rather than the tumor itself, this biomarker could have broad applicability across various cancer types. To explore its versatility, Dr. Ito and his colleagues intend to investigate whether CX3CR1 can predict treatment response to other forms of immunotherapy, such as adoptive T-cell therapy and vaccine-based therapy.

The research team plans to expand their investigation by gathering additional evidence from a larger cohort of NSCLC patients undergoing ICI therapy, both with and without chemotherapy. If subsequent studies yield positive results, a blood test for CX3CR1 as a biomarker could potentially become available to a wider range of patients within the next two to three years.

Aside from Dr. Ito, the study’s co-authors include Takayoshi Yamauchi from the Keck School of Medicine of USC, Eihab Abdelfatah from New York University Langone Health, and Mark D. Long, Ryutaro Kajihara, and Takaaki Oba from the Roswell Park Comprehensive Cancer Center. Their collaborative efforts contribute to advancing our understanding of personalized cancer treatment and paving the way for more targeted therapies based on individual patient characteristics.

Source: Keck School of Medicine of USC

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