Professor Kunisaki Yuya Fukuoka, Japan \u2013 Medical researchers in Japan have discovered a way to predict a potentially life-threatening side effect of cancer immunotherapy before it occurs. By analyzing cerebrospinal fluid collected pre-treatment, researchers at Kyushu University identified specific proteins associated with a damaging immune response that can affect the central nervous system after therapy. Their findings, published in Leukemia<\/a> on 11 March, 2025, could make immunotherapy cancer treatment safer by helping doctors identify high-risk patients in advance, allowing early treatment or even prevention of this condition.<\/p>\n Over the past decade, cancer immunotherapy\u2014where the patient\u2019s immune system is used to fight cancer\u2014has become a promising new treatment strategy. One form of immunotherapy, called CAR-T-cell therapy, uses genetic engineering to reprogram a patient\u2019s immune cells (T cells) to target and destroy cancer cells. It has proven successful in treating blood cancers but comes with serious risks, including immune effector cell-associated neurotoxicity syndrome (ICANS), which causes inflammation in the central nervous system.<\/p>\n \u201cICANS can present with mild symptoms, such as headache or lethargy, but in more severe cases it can be life-threatening, with patients experiencing impaired consciousness, seizures or bleeding in the brain,\u201d says Dr. Yuya Kunisaki<\/a>, a professor in the Department of Clinical Chemistry and Laboratory Medicine<\/a>, Kyushu University Hospital<\/a>. \u201cThe incidence rate of ICANS after CAR-T therapy is very high, around 64%, but until now, there hasn\u2019t been a reliable way to predict ICANS severity.\u201d<\/p>\n In this study, the research team analyzed the proteins in leftover cerebrospinal fluid taken from 29 patients with B-cell non-Hodgkin\u2019s lymphoma before they received CAR T therapy. Within that cohort, 11 patients developed ICANS while 18 patients did not.<\/p>\n The research team identified 864 proteins present in all spinal fluid samples. From there, they narrowed the list down to 46 proteins that showed clear differences in levels between patients who developed ICANS and those who did not, making them potential biomarkers for predicting the condition.<\/p>\n Ultimately, the researchers found that C1RL, a protein with elevated levels in ICANS patients, and FUCA2, a protein with lower levels in ICANS patients, were the best predictors. When looking at these proteins together, a predictive test determined their ratio had high accuracy in distinguishing patients at high risk of ICANS from those at low risk.<\/p>\n The team then tested the C1RL\/FUCA2 biomarker on a second group of 10 patients undergoing CAR-T therapy and found that for all patients, the protein ratio correctly determined the risk of developing ICANS. <\/p>\n However, the researchers cautioned that despite its high accuracy, the study\u2019s small sample size means their findings are still preliminary. \u201cWe now need to conduct the study with a larger number of patients to fully validate our results,\u201d says co-first author, Dr. Tomoko Nomiyama, a clinical technologist in the Department of Clinical Chemistry and Laboratory Medicine, Kyushu University Hospital.<\/p>\n In addition to helping doctors detect ICANS early and start treatment sooner, the researchers hope that identifying key biomarkers will allow doctors to give preventive drugs before CAR-T therapy begins, reducing the risk of ICANS developing at all. For example, C1RL, which is elevated in ICANS patients, is involved in the complement system\u2014a part of the immune system that is known to cause inflammation and may contribute to ICANS.<\/p>\n \u201cIf the biomarker ratio shows a patient is at high risk for ICANS, we could preemptively treat them with drugs that inhibit the complement system to lower the risk,\u201d explains Kunisaki. \u201cThis predictive test could therefore pave the way for a more personalized and safer approach to cancer treatment.\u201d<\/p>\n The research team also plans to test if these biomarkers are accurate for patients with other blood cancers beyond B-cell non-Hodgkin\u2019s lymphoma. Finally, they are also widening their search, hoping to uncover key biomarkers in more easily collected fluids, like blood serum.<\/p>\n \u201cSpinal fluid collection is an invasive and painful procedure, so most hospitals in Japan and other countries don\u2019t routinely perform it before CAR-T therapy,\u201d says Nomiyama. \u201cIf we can identify similar biomarkers in blood, our test would become a much simpler and more accessible tool for predicting ICANS.\u201d<\/p>\n Kunisaki Yuya, Professor<\/a>
\nFaculty of Medical Sciences<\/span><\/strong><\/p>\nResearch-related inquiries<\/h4>\n
\nFaculty of Medical Sciences<\/a>
\nContact information can also be found in the full release<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"Certain proteins in cerebrospinal fluid could act as key indicators for a harmful side effect of cancer immunotherapy, offering hope for early treatment or even prevention of this neurotoxic condition. Professor Kunisaki Yuya Faculty of Medical Sciences Fukuoka, Japan \u2013 Medical researchers in Japan have discovered a way to predict a potentially life-threatening side effect […]","protected":false},"author":7,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":[],"categories":[23],"tags":[43],"acf":[],"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/sdgs.kyushu-u.ac.jp\/en\/wp-json\/wp\/v2\/posts\/25025"}],"collection":[{"href":"https:\/\/sdgs.kyushu-u.ac.jp\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/sdgs.kyushu-u.ac.jp\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/sdgs.kyushu-u.ac.jp\/en\/wp-json\/wp\/v2\/users\/7"}],"replies":[{"embeddable":true,"href":"https:\/\/sdgs.kyushu-u.ac.jp\/en\/wp-json\/wp\/v2\/comments?post=25025"}],"version-history":[{"count":6,"href":"https:\/\/sdgs.kyushu-u.ac.jp\/en\/wp-json\/wp\/v2\/posts\/25025\/revisions"}],"predecessor-version":[{"id":25037,"href":"https:\/\/sdgs.kyushu-u.ac.jp\/en\/wp-json\/wp\/v2\/posts\/25025\/revisions\/25037"}],"wp:attachment":[{"href":"https:\/\/sdgs.kyushu-u.ac.jp\/en\/wp-json\/wp\/v2\/media?parent=25025"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sdgs.kyushu-u.ac.jp\/en\/wp-json\/wp\/v2\/categories?post=25025"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sdgs.kyushu-u.ac.jp\/en\/wp-json\/wp\/v2\/tags?post=25025"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}