Efficient Biomarker for Immunotherapy: Measuring Broad\nClones Effector Tumor Antigen-Specific T Cells in the Blood of Esophageal\nCancer Patients

Cancer\nis the result of the interactions between tumor cells and\ntumor-specific immune responses. The current biomarkers detect tumor\ncells’ properties, but accurate measurement of tumor-specific\nimmunity is lacking. Most immunotherapies work by activating new effector\ntumor antigen-specific T cells (ETASTs) or reactivating pre-existing\nETASTs’ repertoire. The responses to immunotherapy depend on\nthe increase of ETASTs. The amount of ETASTs, especially in blood,\nis critical for therapeutic efficacy. Distinguishing ETASTs from other\nT cells by their structural characteristics is difficult. Therefore,\nnanoparticles loading whole tumor antigens are utilized to activate\nbroad clones ETASTs pre-existing in peripheral blood, followed by\ndetecting them. Thus, the differences between ETASTs and other T cells\nare transformed to the differences between activated states and unactivated\nstates. By measuring the markers of activated states and cytotoxic\nfunctions, we can distinguish ETASTs from other T cells. Nanoparticles\nloading mixed multiple allogeneic tumor tissue lysates or mixed multiple\ntumor cell lines can be utilized as universal nanoparticles to replace\nnanoparticles loading personalized tumor tissue. ETASTs (TATAN-activated\nCD8<sup>+</sup>IFN-γ<sup>+</sup>) in esophageal cancer patients\nare more than those in healthy people. Measurement of the ETASTs in\nthe blood of esophageal cancer patients before and after ongoing therapy\nshowed that ETATSs increased in the blood of patients who were responsive\nto immunotherapy but did not increase in the blood of nonresponders.\nThese illustrated that therapeutic efficacy was positively correlated\nwith the level of ETASTs in PBMC. Altogether, this study provides\nus a highly accurate and specific biomarker for predicting the therapeutic\nefficacy of cancer immunotherapy and potentially other therapies,\nsuch as radiotherapy.