Phototherapy Facilitates Tumor Recruitment and Activation of Natural Killer T cells for Potent Cancer Immunotherapy
Min Li, Di Xie, Xinfeng Tang, Yang Chen, Yanqiong Shen, Han Zhou, Wuxian Deng, Jiwei Liu, Shanbao Cai, Li Bai, Yucai Wang
Abstract
Adoptively transferred natural killer T (NKT) cells confer distinct cancer surveillance without causing obvious side effects, making them a promising candidate for cancer immunotherapy. However, their therapeutic efficacy is limited by inefficient tumor infiltration and inadequate activation in an immunosuppressive tumor microenvironment. To overcome these obstacles, we develop a strategy of using photothermal therapy (PTT) to promote the antitumor ability of adoptively transferred NKT cells. The transferred NKT cells are efficiently recruited to PTT-treated tumors in response to PTT-created inflammation. Moreover, PTT treatment promotes the activation of NKT cells and enhances the NKT cell-initiated immune cascade. As a consequence, the combined therapy of PTT plus NKT cell transfer exhibits excellent growth inhibition of local tumors. Moreover, it efficiently rejects distant tumors and elicits long-term immunological memory to prevent tumor recurrence. Overall, the current study opens new paths to the clinical translation of NKT cells for cancer immunotherapy.