Kehua Jiang,1,* Hongming Liu,2,* Xiaolong Chen,1 Zhen Wang,1 Xiaodong Wang,1 Xiaoya Gu,3 Yonghua Tong,4 Xiaozhuo Ba,4 Yu He,4 Jian Wu,4 Wen Deng,4 Qing Wang,1 Kun Tang4,5 

1Department of Urology, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, People’s Republic of China; 2Department of Urology, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 3Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, People’s Republic of China; 4Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 5Shenzhen Huazhong University of Science and Technology Research Institute, Shenzhen, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Kun Tang, Email tangsk1990@163.com Qing Wang, Email wangqing1@gz5055.com

Abstract: Although immunotherapy has made significant progress in cancer treatment, its limited responsiveness has greatly hindered widespread clinical application. The Warburg effect in tumor cells creates a tumor microenvironment (TME) characterized by hypoxia, low glucose levels, and high lactate levels, which severely inhibits the antitumor immune response. Consequently, targeting glucose metabolism to reprogram the TME is considered an effective strategy for reversing immunosuppression and immune evasion. Numerous studies have been conducted on enhancing cancer immunotherapy efficacy through the delivery of glucose metabolism modulators via nanocarriers. This review provides a comprehensive overview of the glucose metabolic characteristics of tumors and their impacts on the immune system, as well as nanodelivery strategies targeting glucose metabolism to enhance immunotherapy. These strategies include inhibiting key glycolytic enzymes, blocking glucose and lactate transporters, and utilizing glucose oxidase and lactate oxidase. Furthermore, this article reviews recent advancements in synergistic antitumor therapy involving glucose metabolism-targeted therapy combined with other treatments, such as chemotherapy, radiotherapy (RT), phototherapy, and immunotherapy. Finally, we discuss the limitations and future prospects of nanotechnology targeting glucose metabolism therapy, hoping to provide new directions and ideas to improve cancer immunotherapy.

Keywords: nanoparticles, glycolysis, lactate metabolism, cancer immunotherapy, tumor microenvironment