2021/09/21
Keio University School of Medicine
A research group from Keio University School of Medicine, led by Research Associate Kiminari Takamatsu, Senior Lecturer Nobuyuki Tanaka, and Professor Mototsugu Oya of the Department of Urology, and Professor Hiroshi Nishihara of the Genomic Medicine Unit, Cancer Center, has developed a new classification for renal cell carcinoma using LAG-3, TIM-3, and TIGIT, which are target molecules for next-generation immune checkpoint inhibitors.
Normally, immune cells in the body recognize and attack cancer cells as foreign objects, thereby eliminating them. However, cancer cells evade attack from immune cells by expressing proteins called immune checkpoint molecules (a cancer immune escape mechanism). Immune checkpoint inhibitors, which block this cancer immune escape mechanism, are used in many cancer treatments, but cases with insufficient therapeutic effects remain a problem. Therefore, next-generation immune checkpoint inhibitors are being developed, and LAG-3, TIM-3, and TIGIT are attracting attention as promising target molecules. The new classification system developed in this study has identified potential candidates for treatment with next-generation immune checkpoint inhibitors. A detailed cellular-level evaluation of LAG-3, TIM-3, and TIGIT expression in renal cell carcinoma cases revealed that each case predominantly expressed one of these three molecules. Detailed analysis of the cancer microenvironment revealed that cases with predominant LAG-3 expression have a weakened immune environment for attacking cancer cells, which was also associated with a poor prognosis. It is hoped that further development of this research will enable the prediction of the efficacy of next-generation immune checkpoint inhibitors, which would not only allow for the delivery of new drugs to patients who will benefit from them but also help to curb rising medical costs.
The results of this research were published online in the British scientific journal "Nature Communications" on September 20, 2021 (British Summer Time).
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