A new non-invasive method can be used to track the progression of a highly-respected anti-cancer immunotherapy. This could change the direction of research in this fieldMany cancer tumors are caused by immunosuppression. This is when they alter biological systems within their microenvironments to signal to specific immune cells, which clear out abnormal cells, to stop working. This is why immunotherapy to restore anti-tumor immunity has become the preferred treatment for these types of cancers.Indoleamine-2.3-dioxygenase 1, a natural immunosuppressive molecule, is able to help cancer tumors. It is found in many cancer tumors including skin, breast, colon and lung. Scientists have started to consider it a promising therapeutic target. All efforts have failed in phase 3 clinical trial, which is when a large number people with the disease test the best dose to determine its effectiveness. What is the reason that something so promising in theory but not in practice ends up failing in clinical trials in the late phase?A team of researchers led by Dr. MingRong Zhang, Director of Advanced Nuclear Medicine Sciences at Japan's National Institutes for Quantum and Radiological Science and Technology (Japan), tried positron emission imaging (PET) imaging in order to track IDO1 activity after possible treatments were administered. Their breakthrough is now published in BMJ's Journal for ImmunoTherapy of Cancer.Dr. Zhang says, "In our paper we highlight the development of our PET imaging technique, from tracer synthesis to biomarker identification to validation in a mouse model for melanoma treated using different immunotherapy regimens."Scientists began by using a radiotracer, which is a chemical that emits radiation and can be detected by machines. It was known to bind with IDO1. After they established that the radiotracer could reliably detect levels of IDO1 expression in specific areas of the body, the scientists went on to investigate whether it can also be used to reflect the different treatment outcomes of three combinations of immunotherapy strategies, each of which involves an IDO1 inhibitor.The radiotracer and therapies were administered to mice with cancerous tumors. They then monitored the progress of the treatments over time using whole-body PET imaging. They were surprised to find that although one treatment strategy was more effective than the other, IDO1 was inhibited much more than the other. However, radiotracer uptake in tumors appeared to be the same for all of them. The radiotracer signal was emitted from the mesenteric lymphode, an organ that is not associated with the tumor. The other treatment strategies did not experience this problem. Further examination revealed that the radiotracer was bound to IDO1 in these lymph nodes. Why is this organ? This is research for another study.The scientists then looked at another checkpoint. Did the peak and trough radiotracer levels in lymph nodes correspond to the maximum tumor inhibition and the decline in treatment effectiveness? The results showed that radiotracer uptake was higher than expected, peaking with maximum treatment efficacy a few days prior to the peak, then plateauing until the beginning of treatment decline. Finally, the radiation stopped when the tumor relapsed.The scientists discovered a novel biomarker that could monitor IDO1 activity non-invasively. This is a promising alternative to invasive biopsy.Dr. Lin Xie, coauthor of the paper, further explained the findings. He said, "Our findings suggest that the IDO1 status within the mesenteric Ly node is an unparalleled surrogate marker for the cancer-immune setting point, which is an optimum state from tumor tolerance and elimination in response to immunotherapeutic interventions.Dr. Kuan Hu, another researcher, said that the study has great potential to be used as a method for visualizing personalized antitumor reactions in patients. This could help address any possible reasons for failures in clinical trials and improve the therapeutic outcomes of IDO1 regimens. Our research also demonstrates a potential precision medicine paradigm that allows noninvasive visualization of each patient’s individual response to combinatorial chemotherapy immunotherapy. This opens up new avenues for future clinical studies for precision anticancer immunotherapies.###Read more:"Off-tumor IDO1 target interactions determine the cancer-immune setting point and predict the immunotherapeutic efficacy."Lin Xie. Kuan Hu. Yanhong Duo. Takashi Shimokawa. Katushi Kumata. Yiding Zhang. Cuiping Jiang. Lulu Zhang. Nobuyuki Naengaki. Hidekatsu Wakizaka. Yihai Cao. Ming-Rong ZhangJournal of ImmunoTherapy of cancer: June 20, 2021 DOI:http://dx. doi. doi. 1136/ jitc-2021 002616About the National Institutes for Quantum and Radiological Science and TechnologyIn April 2016, the National Institutes for Quantum and Radiological Science and Technology was created to promote and integrate quantum science and technology. QST's mission consists of advancing quantum and radiological sciences through research and development. It is committed to the advancement of quantum science and technology, radiation emergency medicine, medical use of radiation, and other related topics. QST strives to create world-leading research platforms and explore new areas in order to ensure that research and innovation has significant academic, socioeconomic, and economic benefits. Website: http:/// / www. Website: https:/// / www. go. go.About Dr. MingRong Zhang, National Institutes for Quantum and Radiological Science and Technology JapanDr. Ming-Rong Zhang is currently the Director of the Department of Advanced Nuclear Medicine Sciences at the Institute for Quantum Medical Science of the National Institutes for Quantum and Radiological Science and Technology. His expertise in molecular imaging and PET chemistry is well-known. He has published over 300 papers in these areas in respected international and national journals. His current research focuses on the detection of immunosuppressive tumours.Information about fundingThis study was supported by JSPS KAKENHI (Grant Nos. 20H03635, JSPS International Joint Research Program (Grant No. JPJSBP120207203 and the Initiative for Realizing Diversity in the Research Environment.Contact Media:Section of Public RelationsDepartment of Management and Planning QSTTel: +81-43-20206-3026 Email info@qst.go.jp
