Efficient Predictor for Immunotherapy Efficacy: Detecting Pan‐Clones Effector Tumor Antigen‐Specific T Cells in Blood by Nanoparticles Loading Whole Tumor Antigens

Abstract Cancer involves tumor cells and tumor‐specific immunity. The ability to accurately quantify tumor‐specific immunity is limited. Most immunotherapies function by activating new effector tumor antigen‐specific T cells (ETASTs) or reactivating the pre‐existing ETASTs repertoire. Therefore, the amount of ETASTs can be used to characterize immunotherapy efficacy. Tumor antigens are highly heterogeneous and detecting most ETASTs is challenging. Therefore, nanoparticles loading whole‐cell tumor antigens are used to activate and detect pan‐clones ETASTs in the blood. The differences between ETASTs and other T cells are transformed into activated and non‐activated states. By measuring markers of the activated status and cytotoxic function of ETASTs, it can distinguish ETASTs from other T cells. ETASTs in patients with lung cancer are higher than those in healthy individuals and those with benign pulmonary nodules. Therapeutic efficacy positively correlated with the number of ETASTs in the blood. ETATS levels increase only in the blood of patients who respond to immunotherapy. Single‐cell sequencing studies validated these findings. This study provides a highly accurate, specific, non‐invasive, and efficient biomarker for predicting immunotherapy efficacy in lung and other cancers. This method can also be applied to evaluate the efficacy of other treatments, such as radiotherapy, oncolytic viruses, and nanomedicine‐based therapies.