Blood-Based Biomarker Enhances Immunotherapy Precision

A subgroup of blood cells has been found by researchers at the Rappaport Family Institute for Research in the Medical Sciences and the Ruth and Bruce Rappaport Faculty of Medicine at the Technion that can predict the outcome of immunotherapy treatment. These results should simplify the process of matching an immunotherapy treatment to a particular patient, as it is critical to predict which patients may respond to a certain treatment. 
Under the direction of Professor Yuval Shaked of the Rappaport Faculty of Medicine, post-doctoral fellow Dr. Tim J. Cooper and doctoral student Madeleine Benguigui led the study that was published in Cancer Cell. They each made an equal contribution to the writing and the study. Pre-clinical cancer models, data analysis, RNA sequencing (scRNA-seq), and human corroboration of the results are the foundations of translational research. 

One of the most significant advances in cancer treatment to date is immunotherapy, which is predicated on the knowledge that the body’s own immune system is highly adept in precisely and selectively attacking cancer cells.  

The issue is that the malignant tumor frequently deceives the immune system, making it unable to recognize the cells as foes. Immunotherapy is founded on the idea that it is better to strengthen the immune system to recognize cancer cells as adversaries and allow the body to recover itself, rather than using chemotherapy medications that damage good tissue in the process of treating cancer.  

Although immunotherapy has been a remarkable success in treating cancer, only about 40% of individuals benefit from this technique. This implies that many patients undergo this severe care ineffectively. Therefore, gaining a thorough understanding of the biological responses to these treatments and identifying biomarkers that can indicate the treatment’s likelihood of success in the future are imperative. 
Biomarkers play a key role in personalized medicine, which assists doctors in developing the best possible treatment plans that are tailored to each patient’s unique needs and medical history. Immunotherapy treatments now include biomarkers, but they are obtained through biopsies, which are intrusive procedures that carry some risk to the patient. Furthermore, this technique has limited predictive power and does not adequately account for the immunological profile unique to that patient. This is the reason that a lot of research in this area, conducted by academics and industry alike, aims to develop novel approaches for predicting which patients would benefit from immunotherapy treatments.  

Researchers at Technion who studied antibody-based immunotherapy found indicators that indicate how a particular patient will react to the medication. These biomarkers don’t need tumor biopsies, which is an invasive operation that isn’t always possible and, as previously noted, can occasionally put the patient in danger. Instead, they exist in the bloodstream.  

In short, the researchers found that malignant growths activate a protein called STING, which in turn triggers the immune system. This activation is particularly strong in cancer cells that will react to immunotherapy treatment. Interferon protein, which is this protein’s manifestation, induces neutrophils to develop into a particular kind that expresses the protein Ly6Ehi.  
These neutrophils stimulate the immune system to target the malignant tumor by acting directly on it. As their presence in the tumor induces greater sensitivity to immunotherapy treatment, the researchers found that these neutrophils may aid in the treatment.  
The researchers deduced that measuring the patient’s blood levels of Ly6Ehi neutrophils might be a useful biomarker for forecasting how the patient would react to immunotherapy. Based on pre-clinical investigations, the researchers evaluated their results on melanoma and lung cancer patients.  
These results are in line with the examination of available information on 1,237 cancer patients treated with antibody-based immunotherapy. As a result, they proved that neutrophils could accurately anticipate how patients will respond to immunotherapy. The technology created by the research group of Prof. Yuval Shaked has been filed for patent and is presently undergoing a tech transfer process with OncoHost to continue development. Prof. Shaked notes that the technology is compatible with the widely used flow cytometry apparatus, which is authorized by regulatory bodies and is present in all hospitals.  

Journal Reference  

Madeleine Benguigui et al, Interferon-stimulated neutrophils as a predictor of immunotherapy response, Cancer Cell (2024). DOI: 10.1016/j.ccell.2023.12.005.